OLIMEL 1000 ML Эмульсия для внутривенного введения

Содержание инструкции

1. OLIMEL
   1. What is OLIMEL PERIFERICO N4E emulsion for infusion and what is it used for?
   2. What you need to know before you are given OLIMEL PERIPHERIC N4E
2. OLIMEL PERIFERICO N4E should not be administered simultaneously with blood
   1. How to use OLIMEL PERIFERICO N4E, emulsion for infusion
   2. Possible side effects
   3. How to store OLIMEL PERIFERICO N4E emulsion for infusion
   4. Package Contents and Other Information
   5. 1,000 mL 1,500 mL 2,000 mL 2,500 mL
3. OLIMEL PERIFERICO N4E can be supplemented with electrolytes, based on the following table:
4. OLIMEL
   1. What is OLIMEL N5E, emulsion for infusion and what is it used for
   2. What you need to know before you are given OLIMEL N5E emulsion for infusion
   3. How to use OLIMEL N5E, emulsion for infusion
   4. Possible side effects
   5. How to store OLIMEL N5E, emulsion for infusion
   6. Contents of the pack and other information
   7. 500 mL 2.000 mL 2.500 mL
5. OLIMEL
   1. WHAT IS OLIMEL N7 AND WHAT IS IT USED FOR
   2. What you need to know before you are given OLIMEL N7 emulsion for infusion
   3. How to use OLIMEL N7, emulsion for infusion
   4. Possible side effects
   5. How to store OLIMEL N7, emulsion for infusion
   6. Contents of the pack and other information
6. OLIMEL N7. For example, pediatric patients may have a requirement greater than
7. OLIMEL
   1. What is OLIMEL N7E, emulsion for infusion and what is it used for
   2. What you need to know before you are given OLIMEL N7E, emulsion for infusion
   3. How to use OLIMEL N7E, emulsion for infusion
   4. POSSIBLE SIDE EFFECTS
   5. How to store OLIMEL N7E emulsion for infusion
   6. Package Contents and Other Information
   7. 1,000 mL 1,500 mL 2,000 mL
8. OLIMEL
   1. What is OLIMEL N9 emulsion for infusion and what is it used for
   2. What you need to know before you are given OLIMEL N9 emulsion for infusion
   3. How to use OLIMEL N9 emulsion for infusion
   4. Possible side effects
   5. How to store OLIMEL N9, emulsion for infusion
   6. Contents of the pack and other information
   7. 1,000 mL 1,500 mL 2,000 mL
9. OLIMEL
   1. What is OLIMEL N9E emulsion for infusion and what is it used for
   2. What you need to know before you are given OLIMEL N9E emulsion for infusion
   3. How to use OLIMEL N9E emulsion for infusion
   4. Possible side effects
   5. How to store OLIMEL N9E emulsion for infusion
   6. Contents of the pack and other information
   7. 1,000 mL 1,500 mL 2,000 mL
10. OLIMEL
    1. What is OLIMEL N12 emulsion for infusion and what it is used for
    2. What you need to know before you are given OLIMEL N12 emulsion for infusion
    3. How to use OLIMEL N12 emulsion for infusion
    4. Possible side effects
    5. How to store OLIMEL N12 emulsion for infusion
    6. Content of the pack and other information
    7. What is OLIMEL N12E emulsion for infusion and what is it used for
    8. What you need to know before you are given OLIMEL N12E emulsion for infusion
    9. How to use OLIMEL N12E emulsion for infusion
    10. Possible side effects
    11. How to store OLIMEL N12E emulsion for infusion
    12. Contents of the pack and other information

OLIMEL

PERIFERICO N4E, Emulsion for Infusion

Read this leaflet carefully before you are given this medicine
as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse. If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet:

• 1. What OLIMEL PERIFERICO N4E emulsion for infusion is and what it is used for
• 2. What you need to know before you are given OLIMEL PERIFERICO N4E emulsion for infusion
• 3. How to use OLIMEL PERIFERICO N4E, emulsion for infusion
• 4. Possible side effects
• 5. How to store OLIMEL PERIFERICO N4E emulsion for infusion
• 6. Contents of the pack and other information

1. What is OLIMEL PERIFERICO N4E emulsion for infusion and what is it used for?

OLIMEL PERIFERICO N4E is an emulsion for infusion. It is presented in the form of a 3
compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion and the third a solution of amino acids with other electrolytes.
OLIMEL PERIFERICO N4E is used to provide nutrition to adults and children over the age of
two years via a tube into a vein, when normal oral feeding is not suitable.
OLIMEL PERIFERICO N4E must be used exclusively under medical supervision.

2. What you need to know before you are given OLIMEL PERIPHERIC N4E

emulsion for infusion
OLIMEL PERIPHERIC N4E,emulsion for infusion must not be used

• In premature newborns, infants and children under 2 years of age. If you are hypersensitive (allergic) to egg proteins, soy seeds, peanuts, or corn/corn-derived products (see also the section “Warnings and precautions” below) or to any of the excipients.
• If the use of certain amino acids creates problems for your body.
• If you have particularly high levels of fats in your blood.
• If you have hyperglycemia (too much sugar in the blood).
• If you have an abnormally high concentration of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood.

In all cases, the doctor will decide whether you should receive this medicine based on factors
such as age, weight and medical condition, together with the results of the tests performed.

Warnings and precautions
Talk to your doctor or nurse before you are given OLIMEL PERIPHERIC N4E.
If you are given total parenteral nutrition solutions too quickly, this can cause injury or death.
The infusion must be stopped immediately if you develop signs or symptoms of an abnormal
allergic reaction (such as sweating, fever, chills, headache, skin rash or
difficulty breathing). This medicine contains soybean oil and egg phospholipids.
Soy seeds and egg proteins can cause hypersensitivity reactions.
Allergic cross-reactions between soy and peanut proteins have been observed.
Olimel Peripheric N4E contains glucose derived from corn, which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section
“OLIMEL PERIPHERIC N4E, emulsion for infusion must not be used” above)
Difficulty breathing may also be a sign that small particles have formed,
which block blood vessels in the lungs (pulmonary vascular precipitates). If you
experience difficulty breathing, tell your doctor or nurse, who will decide what
actions to take.
The antibiotic called ceftriaxone must not be mixed or administered
simultaneously with any solution containing calcium (including OLIMEL PERIPHERIC
N4E) that is given to you by intravenous infusion.
These medicines must not be given together even through different infusion lines or different infusion sites.
However, you may take OLIMEL PERIPHERIC N4E and ceftriaxone sequentially, one after
the other, if different infusion lines are used or if the infusion lines are
replaced or thoroughly washed with saline between infusions to avoid the formation of precipitates (calcium-ceftriaxone salt particles).
Some medicines and diseases can increase the risk of developing infection or sepsis (bacteria
in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. The doctor will monitor you carefully for any
signs of infection. Patients who require parenteral nutrition (nutrition through
a tube placed in a vein) may be at increased risk of developing infections from their
medical conditions. The use of aseptic techniques (germ-free) during catheter placement and
maintenance and during the preparation of the nutritional formula
(total parenteral nutrition) can reduce this risk.
If you are severely malnourished, to the point of receiving nutrition intravenously,
the doctor must start treatment slowly. In addition, the doctor must monitor you
carefully to prevent sudden changes in your fluid levels, vitamins,
electrolytes and minerals.
The balance of water and salt in your body and metabolic disorders will be corrected
before starting the infusion. The doctor will monitor your condition while you receive this
medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and
trace elements, if they deem it necessary.
The doctor must be informed in case of:

• severe kidney problem. You must inform the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment;
• severe liver problem;
• coagulation problem;
• inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangular glands located above the kidneys;
• heart failure;
• lung disease;
• accumulation of water in the body (hyperhydration);
• insufficient water in the body (dehydration);
• untreated high blood sugar levels (diabetes mellitus);
• heart attack or stroke secondary to sudden heart failure;
• severe metabolic acidosis (when the blood is too acidic);
• generalized infection (septicemia);
• coma.

To verify the effectiveness and overall safety of administration, the doctor will perform
clinical and laboratory tests while you receive this medicine. If you are given
this medicine for several weeks, your blood will be monitored regularly.
The reduced ability of the body to remove the fats contained in this medicine can
cause a “fat overload syndrome” (see section 4 - Possible side effects).
If you experience pain, burning or swelling at the infusion site or leakage of the
infusion solution during the infusion, tell your doctor or nurse. The administration will
be stopped immediately and restarted in another vein.
If your blood sugar level becomes too high, the doctor will adjust the rate of
delivery of OLIMEL PERIPHERIC N4E or give you a medicine to control your blood sugar level (insulin).
OLIMEL PERIPHERIC N4E can be given to you through a tube (catheter) in a vein
in your arm or in a large vein in your chest (central vein).

Children and adolescents
If the patient is under 18 years of age, particular attention will be paid to providing the
correct dosage. Greater precautions will also be taken for the increased sensitivity
of children to the risk of infection. Supplementation with vitamins and trace elements is always
required. Pediatric formulations should be used.

Other medicines andOLIMEL PERIPHERIC N4E
Tell your doctor if you are taking or using, have recently taken or used, or might
take or use any other medicine.
The simultaneous assimilation of other medicines is generally not a
contraindication. If you are taking other medicines, with or without a prescription, inform
your doctor in advance to verify their compatibility.

OLIMEL PERIFERICO N4E should not be administered simultaneously with blood

through the same infusion set.
OLIMEL PERIFERICO N4E contains calcium. It should not be administered together
with the antibiotic ceftriaxone or through the same tube, because particles may form. If the same device is used to administer these medicines in
succession, the device must be thoroughly washed.
Due to the risk of precipitation, OLIMEL Periferico N4E should not be administered
through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic
fosphenytoin.
The olive and soybean oils in OLIMEL PERIFERICO N4E contain vitamin K. This
vitamin generally does not affect blood-thinning medications (anticoagulants),
such as coumarin. However, inform your doctor if you are taking anticoagulant drugs.
The lipids contained in this emulsion may interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your
blood (which are usually eliminated after a period of 5 or 6 hours without receiving them).
OLIMEL PERIFERICO N4E contains potassium. Take particular care with patients who
are taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (drugs
for the treatment of hypertension) or immunosuppressants. These types of drugs may
increase potassium levels in the blood.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are
breastfeeding, ask your doctor for advice before taking this
medicine.
OLIMEL PERIFERICO N4E may be considered during pregnancy and
breastfeeding if necessary.

Driving and operating machinery
Not relevant

3. How to use OLIMEL PERIFERICO N4E, emulsion for infusion

Dosage
OLIMEL PERIFERICO N4E must be administered only to adults and children over the age of
two years.
This is an emulsion for infusion, to be administered via a tube (catheter)
into a vein in the arm or into a large vein in the chest.
OLIMEL PERIFERICO N4E must be at room temperature before use.
OLIMEL PERIFERICO N4E is for single use only.
The infusion of a bag usually lasts between 12 and 24 hours.

Dosage - Adults
The doctor will specify a flow rate corresponding to Your needs and clinical
conditions.
The prescription may continue for as long as required, according to Your clinical
conditions.

Dosage - Children over two years of age and adolescents
The doctor will decide the dose and for how long the medicine will be administered. This
will depend on age, weight, height, medical conditions and the body's ability to break down and use the components of OLIMEL PERIFERICO N4E.

If you have been given more OLIMEL PERIFERICO N4E, emulsion for infusion, than
you should
If the dose given is too high or the infusion is too fast, the amino acid content may
make your blood too acidic and symptoms of hypervolemia (increased
blood volume) may occur. Blood and urine glucose levels may
increase and a hyperosmolar syndrome (excessive blood viscosity) may develop and
the lipid content may increase the level of triglycerides in your blood. Receiving
an infusion too quickly or too large a volume of OLIMEL PERIFERICO N4E can
cause nausea, vomiting, chills, headache, hot flashes, excessive sweating (hyperhidrosis)
and electrolyte disturbances. In such situations the infusion must be stopped
immediately.
In some severe cases, the doctor may temporarily subject you to renal dialysis to help
your kidneys eliminate the excess product.
To prevent such events from occurring, the doctor will regularly check your condition
and test your blood parameters.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any changes in the way you feel, during or after treatment, tell your doctor or
nurse promptly.
The tests that your doctor will perform while you are taking the medicine reduce the risk of side
effects.
The infusion will be stopped immediately if signs or symptoms of an allergic reaction develop, such as
sweating, fever, chills, headache, skin rash or difficulty breathing.
With OLIMEL PERIFERICO N4E the following side effects have been reported:

Frequency - Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia).
• Decreased appetite.
• Increased level of fats in the blood (hypertriglyceridaemia).
• Abdominal pain.
• Diarrhoea.
• Nausea.
• Increased blood pressure (hypertension).

Frequency - Not known: frequency cannot be estimated from the available data

• Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation,
  swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles,
  inflammation, thickening or constriction of the skin at the infusion site.

The following side effects have been reported with similar parenteral nutrition products:

Frequency- Very rare: may affect up to 1 in 10,000 people

• Reduced ability to remove lipids (fat overload syndrome) associated with a sudden and sharp
  deterioration of the patient's medical condition. The following symptoms of fat overload syndrome are
  usually reversible after stopping the lipid emulsion infusion:
• 1. Fever
• 2. Reduction of red blood cells which can make the skin pale and cause weakness or shortness of
  breath (anaemia).
• 3. Low white blood cell count, which can increase the risk of infection (leucopenia)
• 4. Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia)
• 5. Blood coagulation disorders that compromise the blood's ability to clot
• 6. High levels of fats in the blood (hyperlipidaemia)
• 7. Hepatic lipid infiltration (hepatomegaly)
• 8. Deterioration of liver function
• 9. Manifestations affecting the central nervous system (e.g., coma).

Frequency - Not known: frequency cannot be estimated from the available data

• Allergic reactions.
• Abnormal blood test results for liver function.
• Problems in the elimination of bile (cholestasis)
• Increased liver size (hepatomegaly).
• Jaundice (icterus).
• Reduced number of platelets (thrombocytopenia).
• Increased levels of nitrogen in the blood (azotaemia).
• Elevated liver enzymes
• Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular
  precipitates) and cause pulmonary embolism and breathing difficulties (respiratory distress).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist.
You can also report side effects directly through the national reporting system at:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa .
By reporting side effects you can help provide more information on the safety of this medicine .

5. How to store OLIMEL PERIFERICO N4E emulsion for infusion

Keep this medicine out of sight and reach of children
Do not use this medicine after the expiry date which is stated on the container and on the
outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What OLIMEL PERIPHERIC N4E, emulsion for infusion contains
The active substancesof each pouch of the reconstituted emulsion are a solution of L-
amino acids 6.3%(corresponding to 6.3 g/100 mL) (alanine, arginine, glycine, histidine,
isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine,
threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid) with electrolytes
(sodium, potassium, magnesium, phosphate, acetate, chloride), a lipid emulsion at15%
(corresponding to 15 g/100 mL) (purified olive oil and purified soybean oil) and a

glucose solution at 18.75%(corresponding to 18.75 g/100 mL) (as glucose
monohydrate) with calcium.

The excipients are:
CompartmentCompartmentCompartment
Lipid emulsionAmino acid solutionGlucose solution
Purified egg phospholipid,
glycerol, sodium oleate, sodium
hydroxide (for pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment),
water for injections
Hydrochloric acid (for
pH adjustment),
water for injections

Appearance of OLIMEL PERIPHERIC N4E, emulsion for infusion and contents of the pack
OLIMEL PERIPHERIC N4E is an emulsion for infusion packaged in a three-compartment pouch.
One compartment contains a lipid emulsion, another compartment a solution of amino acids
with electrolytes and the third compartment a glucose solution with calcium. These
compartments are separated by non-permanent membranes.
Before administration, the contents of the compartments must be mixed by rolling the
pouch on itself starting from the top until the membranes open.
Appearance before reconstitution:

• The amino acid and glucose solutions are clear, clear colorless or slightly yellow.
• The lipid emulsion is homogeneous with a milky appearance.

Appearance after reconstitution: homogeneous emulsion with a milky appearance
The 3-compartment pouch is a multi-layer plastic pouch. The material of the inner (contact)
layer of the pouch is designed to be compatible with the constituents and authorized
additives.
To prevent contact with atmospheric oxygen, the pouch is packaged in an outer barrier
packaging for oxygen, which contains an oxygen absorber sachet.

Pack sizes:
1,000 mL pouch: 1 box with 6 pouches
1,500 mL pouch: 1 box with 4 pouches
2,000 mL pouch: 1 box with 4 pouches
2,500 mL pouch: 1 box with 2 pouches
1 pouch of 1,000 mL, 1,500 mL, 2,000 mL and 2,500 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Baxter S.p.A.
Piazzale dell’Industria 20
00144 Rome
Italy

Manufacturer:
Baxter S.A.,
Boulevard René Branquart, 80,
7860 Lessines –
Belgium

This medicinal product is authorised in the member states of the European economic
community with the following names:
France, Portugal, Bulgaria, Romania, Czech Republic, Belgium, Spain, Slovak Republic,
Luxembourg, Slovenia: PERIOLIMEL N4E
Estonia, Poland, Lithuania, Latvia, Greece, Cyprus: OLIMEL PERI N4E
Netherlands: Olimel Perifeer N4E
Austria: PeriOLIMEL 2,5 % mit Elektrolyten
Germany: Olimel Peri 2,5% E
Denmark, Iceland, Sweden, Norway, Finland: Olimel Perifer N4E
United Kingdom, Ireland, Malta: Triomel Peripheral 4g/L nitrogen 700 kcal/L with electrolytes
Hungary: PeriOlimel 4 g/L nitrogén elektrolitokkal emulziós infúzió
 --------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations
ATC code: B05 BA10

• A.QUALITATIVE AND QUANTITATIVE COMPOSITION

OLIMEL PERIPHERIC N4E is presented as a 3-compartment pouch.
Each pouch contains a glucose solution with calcium, a lipid emulsion and an amino acid
solution with other electrolytes:

Content per pouch

1,000 mL 1,500 mL 2,000 mL 2,500 mL

Glucose solution 18.75 %
(corresponding to 18.75 g/100
mL)
400 mL 600 mL 800 mL 1,000 mL
Amino acid solution 6.3 %
(corresponding to 6.3 g/100 mL)
400 mL 600 mL 800 mL 1,000 mL
Lipid emulsion 15 %
(corresponding to 15 g/100 mL)
200 mL 300 mL 400 mL 500 mL
Composition of the reconstituted emulsion after mixing the contents of the three
compartments:

Active ingredients1,000 mL1,500 mL2,000 mL2,500 mL
Purified olive oil + purified soybean oil
30.00 g 45.00 g 60.00 g 75.00 g
Alanine 3.66 g 5.50 g 7.33 g 9.16 g
Arginine 2.48 g 3.72 g 4.96 g 6.20 g
Aspartic acid 0.73 g 1.10 g 1.46 g 1.83 g
Glutamic acid 1.26 g 1.90 g 2.53 g 3.16 g
Glycine 1.76 g 2.63 g 3.51 g 4.39 g
Histidine 1.51 g 2.26 g 3.02 g 3.77 g
Isoleucine 1.26 g 1.90 g 2.53 g 3.16 g
Leucine 1.76 g 2.63 g 3.51 g 4.39 g
Lysine
(equivalent to lysine acetate)
1.99 g
(2.81g)

• 2.99 g (4.21 g) 3.98 g (5.62 g) 4.98 g (7.02 g)

Methionine 1.26 g 1.90 g 2.53 g 3.16 g
Phenylalanine 1.76 g 2.63 g 3.51 g 4.39 g
Proline 1.51 g 2.26 g 3.02 g 3.77 g
Serine 1.00 g 1.50 g 2.00 g 2.50 g
Threonine 1.26 g 1.90 g 2.53 g 3.16 g
Tryptophan 0.42 g 0.64 g 0.85 g 1.06 g
Tyrosine 0.06 g 0.10 g 0.13 g 0.16 g
Valine 1.62 g 2.43 g 3.24 g 4.05 g
Sodium acetate, trihydrate 1.16 g 1.73 g 2.31 g 2.89 g
Sodium glycerophosphate, hydrate 1.91 g 2.87 g 3.82 g 4.78 g
Potassium chloride 1.19 g 1.79 g 2.38 g 2.98 g
Magnesium chloride, hexahydrate 0.45 g 0.67 g 0.90 g 1.12 g
Calcium chloride, dihydrate 0.30 g 0.44 g 0.59 g 0.74 g
Anhydrous glucose
(equivalent to glucose monohydrate)
187.50 g
(206.50 g)
75.00 g
(82.50 g)
112.50 g
(123.75 g)
150.00 g
(165.00 g)
A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%)
corresponding to an essential fatty acids / total fatty acids ratio of 20%.

The excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution
Compartment
Glucose solution
Purified egg phospholipid,
glycerol, sodium oleate, sodium
hydroxide (for pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment),
water for
injections
Hydrochloric acid (for
pH adjustment),
water for
injections
Nutritional contribution of the reconstituted emulsion for each bag size:

Includes calories from purified egg phospholipids
Includes phosphate provided by the lipid emulsion

• B. DOSAGE AND ADMINISTRATION

Dosage
OLIMEL PERIPHERIC N4E is not recommended in children under 2 years of age due to the
inadequate composition and volume (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose reported below. Due to the static composition
of the multi-compartment bag, it may not be possible to simultaneously meet all of the
patient's nutritional needs. Clinical situations may occur in which patients require varying
amounts of nutrients compared to the composition of the static bag. In such a situation,
any adjustment of the volume (dose) must take into account the resulting effect this will have
on the dosage of all other nutrients in OLIMEL PERIPHERIC N4E. For example, pediatric
patients may have a requirement greater than 0.2 mmol/kg/day of phosphate. In these
circumstances, healthcare professionals may consider adjusting the volume (dose) of
OLIMEL PERIPHERIC N4E in order to meet this increased requirement.

In adults:
The dosage depends on energy expenditure, clinical status, body weight and the
patient's ability to metabolize the constituents of OLIMEL PERIPHERIC N4E, as well as
further energy or protein provided orally/enterally, therefore the bag sizes must be chosen
accordingly.
Average daily requirements are:

• 0.16-0.35 g nitrogen/kg body weight (1-2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress,
• 20-40 kcal/kg,
• 20-40 mL fluids /kg or 1-1.5 mL per kcal spent.

For OLIMEL PERIPHERIC N4E, the maximum daily dose is defined by the fluid intake, 40
mL/kg, corresponding to 1 g/kg amino acids, 3 g/kg glucose, 1.2 g/kg lipids, 0.8 mmol/kg
sodium and 0.6 mmol/kg of potassium. For a 70 kg patient, this would be equivalent to
2800 mL OLIMEL PERIPHERIC N4E per day, which translates to an intake of 71 g
amino acids, 210 g glucose and 84 g lipids, or 1680 non-protein kcal and 1960 total kcal.

Normally, the flow rate should be increased gradually during the first
hour and then adjusted to account for the dose to be administered, the volumes to be
taken daily and the duration of the infusion.
For OLIMEL PERIPHERIC N4E, the maximum infusion rate is 3.2 mL/kg/hour, corresponding
to 0.08 g/kg/hour for amino acids, 0.24 g/kg/hour for glucose and 0.10 g/kg/hour for lipids.

In children over 2 years of age
No studies have been conducted in the pediatric population.
The dosage depends on energy expenditure, clinical status, body weight and the
patient's ability to metabolize the constituents of OLIMEL PERIPHERIC N4E, as well as
further energy or protein provided orally/enterally, therefore, the bag sizes
must be chosen accordingly.
Furthermore, daily fluid, nitrogen and energy requirements gradually decrease with
age.
Two groups were considered, age between 2 and 11 years, and age between 12 and 18 years.
For Olimel PERIPHERIC N4E, the limiting factors for the above pediatric groups are the
phosphate concentration for the daily dose (0.2 mmol/kg/day) and the lipid concentration for the hourly rate, resulting in the following intakes:

a: Values recommended by the 2005 ESPGHAN/ ESPEN Guidelines
Normally, the flow rate should be increased gradually during the first
hour and then adjusted taking into account the dose to be administered,
the daily volume intake and the duration of the infusion.
In general, in young children it is recommended to start the infusion with a low daily dose,
and to increase it gradually up to the maximum dosage (see above).
Method and duration of administration
For single use only.
It is recommended to use the contents of the bag immediately after opening and not
to store it for a subsequent infusion.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on preparation and handling of the infusion emulsion, see
section 6.6.
Due to its low osmolarity, OLIMEL PERIPHERIC N4E can be administered via peripheral or
central vein.
The recommended duration of infusion for a bag for parenteral nutrition is between
12 and 24 hours.
Treatment with parenteral nutrition can continue for as long as required by the
patient's clinical condition.

• C.INCOMPATIBILITIES

Do not add any other medicinal product or other substances to any of the constituents of the bag or
to the reconstituted emulsion without first verifying the compatibility and stability of the
resulting preparation (in particular the stability of the lipid emulsion).
Incompatibilities may arise, for example, from excessive acidity (low pH) or from
inadequate content of divalent cations (Ca and Mg) which can destabilize
the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered.
Excessive addition of calcium and phosphate, in particular in the form of mineral salts, can cause
the formation of calcium phosphate precipitates.
OLIMEL Peripheric N4E contains calcium ions which represent a further risk of
coagulation in blood or in anticoagulated or preserved blood components with citrate.
Ceftriaxone must not be mixed or administered concomitantly with intravenous solutions
containing calcium, including OLIMEL Peripheric N4E, through the same infusion line (e.g. via a
Y-connector) due to the risk of ceftriaxone-calcium salt precipitation (see sections 4.4 and 4.5 of the
SmPC). Ceftriaxone and solutions containing calcium can be administered sequentially if different
infusion lines are used or if the infusion lines are thoroughly flushed with saline between infusions to
avoid the formation of precipitates.
Due to the risk of precipitation, OLIMEL Peripheric N4E must not be administered
through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic
phenytoin.
Verify the compatibility with solutions administered simultaneously through the
same administration set, catheter or cannula.
Do not administer before, concurrently or after a blood transfusion through the
same line, due to the risk of pseudoagglutination.

• D.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING

An overview of the various stages of preparation for the administration of OLIMEL
Peripheric N4E is illustrated in Figure 1 .
Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use
only if the bag is undamaged, if the non-permanent separation membranes are
intact (i.e. there is no mixing of the contents of the 3 compartments), if the
amino acid solution and the glucose solution are clear, colorless or slightly yellow,
and practically free from visible particles, and if the lipid emulsion is a homogeneous liquid with
a milky appearance.
Mixing of the solutions and the emulsion
Ensure that the product is at room temperature when breaking the non-permanent separation membranes.
Roll the bag manually on itself, starting from the top (end with loop). The non-permanent
separation membranes will disappear on the side next to the openings. Continue to roll the bag until
the separation membranes are open for about half their length.
Mix the bag by inverting it at least 3 times.
After reconstitution the mixture is a homogeneous emulsion with a milky appearance.
Additives:
The bag is equipped with sufficient capacity to allow additives, such as vitamins, electrolytes
and trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening
the non-permanent separation membranes and after mixing the contents of the
three compartments).
Vitamins can also be added to the glucose compartment before the mixture
is reconstituted (before opening the non-permanent separation membranes and before
mixing the three compartments).
When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag must be considered
Additives must be carried out by qualified personnel under aseptic conditions.

OLIMEL PERIFERICO N4E can be supplemented with electrolytes, based on the following table:

Value corresponding to the addition of inorganic phosphate
Including the phosphate provided by the lipid emulsion

Trace elements and vitamins:
Stability has been demonstrated with commercially available vitamin and trace element preparations
(containing a maximum of 1 mg of iron).
Compatibility of other additives is available upon request.
When making additions, before peripheral vein administration, measure
the final osmolarity of the mixture.
To make an addition:

• the operation must take place under aseptic conditions.
• Prepare the injection site of the bag.
• Puncture the injection site and inject the additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the additions.

Infusion preparation
The operation must take place under aseptic conditions.
Suspend the bag.
Remove the plastic protection from the administration port.
Firmly insert the infusion set spike into the administration port.

1 2 3

4 5 6
Administration
For single use only.
Administer the product only after breaking the non-permanent separation membranes between the 3 compartments and mixing the contents of the 3 compartments.
Ensure that the final emulsion for infusion does not show evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store
the open bag for a subsequent infusion.
Do not reconnect any partially used bags.
Do not connect the bags in series to avoid the possibility of gas embolism due to gas
contained in the main bag.
Dispose of any unused product, any derived waste, and all necessary devices.
Extravasation
The catheter site must be checked regularly for possible signs of
extravasation.
In case of extravasation, administration must be stopped immediately
while keeping the catheter or cannula inserted for immediate patient treatment. If
possible, perform an aspiration through the inserted catheter or cannula to reduce the
amount of fluid present in the tissues before removing the catheter or cannula. If the
extravasation affects a limb, it should be elevated.
Depending on the extravasated product (including one or more products mixed with OLIMEL
Periferico N4E, if applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken. Treatment options may include
non-pharmacological, pharmacological and/or surgical intervention. In case of large-scale
extravasation, consult a plastic surgeon within the first 72 hours.
The extravasation site should be monitored at least every 4 hours during the first 24
hours, then once a day.
The infusion should not be restarted in the same peripheral or central vein.

OLIMEL

N5E, Emulsion for Infusion

Read this leaflet carefully before you are given this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

• 7. What OLIMEL N5E emulsion for infusion is and what it is used for
• 8. What you need to know before you are given OLIMEL N5E emulsion for infusion
• 9. How to use OLIMEL N5E, emulsion for infusion
• 10. Possible side effects
• 11. How to store OLIMEL N5E emulsion for infusion
• 12. Contents of the pack and other information

1. What is OLIMEL N5E, emulsion for infusion and what is it used for

OLIMEL N5E is an emulsion for infusion. It is presented in the form of a 3-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion and the
third a solution of amino acids with other electrolytes.
OLIMEL N5E is used to provide nutrition to adults and children over two years of age through
a tube into a vein, when normal oral feeding is not suitable.
OLIMEL N5E must be used exclusively under medical supervision.

2. What you need to know before you are given OLIMEL N5E emulsion for infusion

OLIMEL N5E, emulsion for infusion must not be used:

• In premature newborns, infants and children under 2 years of age
• If you are hypersensitive (allergic) to egg proteins, soy seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the excipients.
• If the use of certain amino acids causes problems for your body.
• If you have particularly high levels of fats in your blood.
• If you suffer from hyperglycemia (too much sugar in the blood)
• If you have an abnormally high concentration of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood.

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of tests performed.

Warnings and precautions
Consult your doctor or nurse before you are given OLIMEL N5E.
If total parenteral nutrition solutions are administered to you too quickly, this can cause injury or death.
The infusion must be stopped immediately if you develop signs or symptoms of an abnormal allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soy seeds and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soy and peanut proteins have been observed.
Olimel N5E contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N5E, emulsion for infusion must not be used” above)
Difficulty breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, report it to your doctor or nurse, who will decide what actions to take.
The antibiotic called ceftriaxone must not be mixed or administered simultaneously with any solution containing calcium (including OLIMEL N5E) that is administered to you via an intravenous drip.
These medicines must not be administered to you even through different infusion lines or different infusion sites.
However, you can take OLIMEL N5E and ceftriaxone in sequence, one after the other, if infusion lines in different sites are used or if the infusion lines are replaced or thoroughly washed with saline solution between infusions to avoid the formation of precipitates (calcium-ceftriaxone salt particles).
Some medicines and diseases can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. Your doctor will carefully monitor you for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may be at greater risk of developing infections from their medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk.
If you are severely malnourished, to the point of receiving nutrition intravenously, your doctor must start treatment slowly. In addition, the doctor must carefully monitor you to prevent sudden changes in your fluid levels, vitamins, electrolytes and minerals.
The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary.
The doctor must be informed in case of:

• severe kidney problem. You must inform the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment;
• severe liver problem;
• blood clotting problem;
• inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys;
• heart failure;
• lung disease;
• water accumulation in the body (hyperhydration);
• insufficient water in the body (dehydration);
• untreated high blood sugar levels (diabetes mellitus);
• heart attack or stroke secondary to sudden heart failure;
• severe metabolic acidosis (when the blood is too acidic);
• generalized infection (septicemia);
• coma.

To verify the effectiveness and overall safety of administration, your doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is provided to you for several weeks, your blood will be monitored regularly.
The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects).
If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, inform your doctor or nurse. The administration will be stopped immediately and restarted in another vein.
If the blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N5E or give you a medicine to control the blood sugar level (insulin).
OLIMEL N5E can only be administered to you through a tube (catheter) into a large vein in the chest (central vein).

Children and adolescents
If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required.

Other medicines andOLIMEL N5E
Tell your doctor if you are taking or using, have recently taken or used, or might take or use any other medicine.
The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility.
OLIMEL N5E must not be administered simultaneously with blood through the same infusion set.
OLIMEL N5E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tube, because particles can form. If you use the same device to administer these medicines in succession, the device must be thoroughly washed.
Due to the risk of precipitation, OLIMEL N5E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.
The olive and soybean oils in OLIMEL N5E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants), such as coumarin. However, inform your doctor if you are taking anticoagulant medicines.
The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids have been eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them).
OLIMEL N5E contains potassium. Exercise particular caution with patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for treating high blood pressure) or immunosuppressants. These types of medicines can increase potassium levels in the blood.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding with breast milk, ask your doctor for advice before taking this medicine.
OLIMEL N5E can be considered during pregnancy and breastfeeding if necessary

Driving and operating machinery
Not relevant

3. How to use OLIMEL N5E, emulsion for infusion

Dosage
OLIMEL N5E must only be administered to adults and children over two years of age.
This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your
chest.
OLIMEL N5E must be at room temperature before use.
OLIMEL N5E is for single use only.
The infusion of 1 bag usually lasts between 12 and 24 hours

Dosage - adults
The doctor will specify a flow rate corresponding to your needs and clinical condition.
The prescription may continue for as long as required, according to your clinical condition.

Dosage - children over two years of age and adolescents
The doctor will decide the dose and for how long the medicine will be administered. This will depend
on age, weight, height, medical conditions and the body's ability to break down and use the
components of OLIMEL N5E.

If you have been given more OLIMEL N5E, emulsion for infusion, than you should
If the dose given is too high or the infusion is too fast, the amino acid content may make your
blood too acidic and symptoms of hypervolemia (increased blood volume) may occur. Blood and urine glucose levels may increase and a
hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase the
level of triglycerides in your blood. Receiving an infusion that is too fast or a volume of
OLIMEL N5E that is too large can cause nausea, vomiting, chills, headache, hot flashes,
excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be
stopped immediately.
In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys
eliminate the excess product.
To prevent such events from happening, the doctor will regularly check your condition and test
your blood parameters.
If you have any doubts about the use of OLIMEL N5E, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any changes in how you feel during or after treatment, tell your doctor or nurse
promptly.
The tests your doctor will perform while you are taking the medicine reduce the risk of side
effects.
The infusion will be stopped immediately if signs or symptoms of an abnormal allergic reaction develop, such as sweating, fever, chills, headache, skin rash or difficulty in
breathing.
With OLIMEL N5E the following side effects have been reported:

Frequency-Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia).
• Decreased appetite.
• Increased levels of fats in the blood (hypertriglyceridemia).
• Abdominal pain.
• Diarrhea.
• Nausea.
• Increased blood pressure (hypertension).

Frequency - Not known: frequency cannot be estimated based on available data

• Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site.

The following side effects have been reported with similar parenteral nutrition products:

Frequency- Very rare: may affect up to 1 in 10,000 people

• Reduced ability to remove lipids (fat overload syndrome) associated with a sudden and sharp deterioration in the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the infusion of the lipid emulsion:
• Fever
• Reduced red blood cells which can make the skin pale and cause weakness or shortness of breath (anemia).
• Low white blood cell count, which can increase the risk of infection (leukopenia)
• Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia)
• Blood clotting disorders that impair the blood's ability to clot
• High levels of fats in the blood (hyperlipidemia)
• Fatty infiltration of the liver (hepatomegaly)
• Worsening of liver function
• Manifestations affecting the central nervous system (e.g., coma).

Frequency - Not known: frequency cannot be estimated based on available data

• Allergic reactions.
• Abnormal blood test results for liver function.
• Problems with bile drainage (cholestasis)
• Increased liver size (hepatomegaly).
• Jaundice (icterus).
• Reduced number of platelets (thrombocytopenia).
• Increased levels of nitrogen in the blood (azotemia).
• Elevated liver enzymes
• Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and breathing difficulties (respiratory distress).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system at: http://www.agenziafarmaco.gov.it/content/come-
segnalare-una-sospetta-reazione-avversa. By reporting side effects you can help
provide more information on the safety of this medicine.

5. How to store OLIMEL N5E, emulsion for infusion

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the container and on the
outer packaging (MM/YYYY). The expiry date refers to the last day of the month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What OLIMEL N5E, emulsion for infusion contains
The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at
8.2%(corresponding to 8.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride), an emulsion of lipids at20%(corresponding to 20.0 g/100 mL) (purified olive oil and
purified soybean oil) and a solution of glucose at 28.75%(corresponding to 28.75 g/100 mL)
(as glucose monohydrate) with calcium.

The excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution
Compartment
Glucose solution
Hydrochloric acid (for
pH adjustment),
water for injections

Appearance of OLIMEL N5E, emulsion for infusion and contents of the pack
OLIMEL N5E is an emulsion for infusion packaged in a three-compartment bag. One
compartment contains a lipid emulsion, another compartment an amino acid solution with
electrolytes and the third compartment a glucose solution with calcium. These
compartments are separated by non-permanent membranes. Before administration, the
contents of the compartments must be mixed by rolling the bag on itself starting
from the top until the membranes open.
Appearance before reconstitution:
Purified egg phosphatide, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections
The amino acid and glucose solutions are clear, clear colorless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: homogeneous emulsion with a milky appearance
The 3-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorized additives.
To prevent contact with atmospheric oxygen, the bag is packaged in an outer barrier packaging with
oxygen barrier, which contains an oxygen absorber sachet.

Pack sizes:
1,500 mL bag: 1 box with 4 bags
2,000 mL bag: 1 box with 4 bags
2,500 mL bag: 1 box with 2 bags
1 bag of 1,500 mL, 2,000 mL and 2,500 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Baxter S.p.A.
Piazzale dell’Industria 20
00144 Rome
Italy

Manufacturer:
Baxter S.A.,
Boulevard René Branquart, 80,
7860 Lessines
Belgium

This medicinal product is authorised in the member states of the European Economic Community with the following
names:
France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium,
Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden,
Norway, Finland, Greece, Cyprus: OLIMEL N5E
Austria: ZentroOLIMEL 3,3 % mit Elektrolyten >
Germany: Olimel 3,3% E
United Kingdom, Ireland, Malta: Triomel 5g/L nitrogen 990 kcal/L with electrolytes
Hungary: Olimel 5 g/L nitrogén elektrolitokkal emulziós infúzió
 --------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations
ATC code: B05 BA10

• C.QUALITATIVE AND QUANTITATIVE COMPOSITION

OLIMEL N5E is presented as a 3-compartment bag.
Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with other electrolytes:

Content per bag

1.500 mL 2.000 mL 2.500 mL

Glucose 28.75% solution
(corresponding to 28.75 g/100 mL)
600 mL 800 mL 1.000 mL
Amino acid 8.2% solution
(corresponding to 8.2 g/100 mL)
600 mL 800 mL 1.000 mL
20% Lipid emulsion
(corresponding to 20 g/100 mL)
300 mL 400 mL 500 mL
Composition of the reconstituted emulsion after mixing the contents of the three compartments:

Active ingredients1.500 mL2.000 mL2.500 mL
Purified olive oil + purified soybean oil 60.00 g 80.00 g 100.00 g
Alanine 7.14 g 9.52 g 11.90 g
Arginine 4.84 g 6.45 g 8.06 g
Aspartic acid 1.43 g 1.90 g 2.38 g
Glutamic acid 2.47 g 3.29 g 4.11 g
Glycine 3.42 g 4.56 g 5.70 g
Histidine 2.95 g 3.93 g 4.91 g
Isoleucine 2.47 g 3.29 g 4.11 g
Leucine 3.42 g 4.56 g 5.70 g
Lysine
(equivalent to lysine acetate)
6.47 g
(9.13g)
Methionine 2.47 g 3.29 g 4.11 g
Phenylalanine 3.42 g 4.56 g 5.70 g
Proline 2.95 g 3.93 g 4.91 g
Serine 1.95 g 2.60 g 3.25 g
Threonine 2.47 g 3.29 g 4.11 g
Tryptophan 0.82 g 1.10 g 1.37 g
Tyrosine 0.13 g 0.17 g 0.21 g
Valine 3.16 g 4.21 g 5.26 g
Sodium acetate, trihydrate 2.24 g 2.99 g 3.74 g
Sodium glycerophosphate hydrate 5.51 g 7.34 g 9.18 g
Potassium chloride 3.35 g 4.47 g 5.59 g
Magnesium chloride, hexahydrate 1.22 g 1.62 g 2.03 g
Calcium chloride, dihydrate 0.77 g 1.03 g 1.29 g
Anhydrous glucose
(equivalent to glucose monohydrate)
3.88 g
(5.48g)
5.18 g
(7.30g)
172.50 g
(189.75 g)
230.00 g
(253.00 g)
287.50 g
(316.25g)
A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%) corresponding
to an essential fatty acids / total fatty acids ratio of 20%.

The excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution
Compartment
Glucose solution
Hydrochloric acid (for
pH adjustment),
water for injections
Nutritional contribution of the reconstituted emulsion for each pouch size
Purified egg phospholipid, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections

Includes calories from purified egg phospholipids
Includes phosphate provided by the lipid emulsion

• D. DOSAGE AND ADMINISTRATION

Dosage
The use of OLIMEL N5E is not recommended in children under 2 years of age due to the inadequate composition
and volume (see sections 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose reported below. Due to the static composition
of the multi-compartment pouch, it may not be possible to simultaneously meet
all of the patient's nutritional needs. Clinical situations may occur in which patients
require varying amounts of nutrients compared to the composition of the static pouch. In such
situations, any adjustment of the volume (dose) must take into consideration the effect
resulting from this on the dosage of all other nutrients in OLIMEL N5E. For example, the
pediatric patients may have a requirement greater than 0.2 mmol/kg/day of phosphate. In these
circumstances, healthcare professionals may consider adjusting the volume
(dose) of OLIMEL N5E in order to meet this increased need.

In adults:
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N5E, as well as the additional energy or protein provided orally/enterally, therefore the pouch sizes must be chosen
accordingly.
Average daily requirements are:

• 0.16-0.35 g nitrogen/kg body weight (1-2 g amino acids/kg), depending on the patient's nutritional status and the degree of catabolic stress,
• 20-40 kcal/kg,
• 20-40 mL fluids /kg or 1-1.5 mL per kcal spent.

For OLIMEL N5E the maximum daily dose is defined by the fluid intake, 40 mL/kg,
corresponding to 1.3 g/kg amino acids, 4.6 g/kg glucose, 1.6 g/kg lipids, 1.4 mmol/kg sodium and 1.2
mmol/kg potassium. For a 70 kg patient this would be equivalent to 2800 mL of OLIMEL N5E per
day, which translates to an intake of 92g amino acids, 322 g glucose and 112 g lipids, (i.e. 2,408
non-protein kcal and 2,772 total kcal).

Normally, the flow rate should be increased gradually during the first hour
then it must be adjusted to take into account the dose to be administered, the volumes to be taken
daily and the duration of the infusion.
For OLIMEL N5E the maximum infusion rate is 2.1 mL/kg/hour, corresponding to 0.07 g/kg/hour
amino acids, 0.24 g/kg/hour glucose and 0.08 g/kg/hour lipids.

In children over two years of age
No studies have been conducted in the pediatric population.
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N5E, as well as additional energy or protein
provided orally/enterally, therefore, the pouch sizes must be chosen accordingly.
In addition, daily fluid, nitrogen and energy needs decrease continuously with age.
2 groups have been considered, age between 2 and 11 years, and age between 12 and 18 years.
For Olimel N5E the limiting factors for the above pediatric groups are the phosphate concentration
for the daily dose (0.2 mmol/kg/day) and the lipid concentration for the rate, resulting in the
following intakes:

a: Values recommended by the 2005 ESPGHAN/ ESPEN Guidelines-
Normally, the flow rate should be increased gradually during the first hour and then
must be adjusted taking into account the dose to be administered, the daily volume
intake and the duration of the infusion.
In general, in young children it is recommended to start the infusion with a low daily dose, and
to increase it gradually up to the maximum dosage (see above).
Method and duration of administration
For single use only.
It is recommended to use the contents immediately after opening the pouch and not
to store it for a subsequent infusion.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on preparation and handling of the infusion emulsion, see paragraph

• 6.6.

Due to its high osmolarity, OLIMEL N5E can only be administered through a central vein.
The recommended infusion duration for a parenteral nutrition pouch is between 12 and 24 hours.
Treatment with parenteral nutrition may continue for as long as required by the patient's clinical condition.

• E.INCOMPATIBILITIESDo not add any other medicine or substances to any of the constituents of the pouch or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular the stability of the lipid emulsion).

Incompatibilities may arise, for example, from excessive acidity (low pH) or from an inadequate content of divalent cations (Ca and Mg) which may destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, especially
in the form of mineral salts, can cause the formation of calcium phosphate precipitates.
OLIMEL N5E contains calcium ions which represent a further risk of coagulation in blood or
in anticoagulated or citrate-preserved blood components.
Ceftriaxone must not be mixed or administered concurrently with intravenous solutions
containing calcium, including OLIMEL N5E, through the same infusion line (e.g. via a
Y-connector) due to the risk of ceftriaxone-calcium salt precipitation (see sections

• 4.4 and 4.5 of the SmPC). Ceftriaxone and solutions containing calcium can be administered sequentially one after the other if different infusion lines are used or if the infusion lines have been thoroughly flushed with saline between infusions to avoid the formation of precipitates. Due to the risk of precipitation, Peripheral OLIMEL N5E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.

Verify compatibility with solutions administered simultaneously through the same
administration set, catheter or cannula.
Do not administer before, concurrently or after a blood transfusion through the same line,
due to the risk of pseudoagglutination.

• F.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLINGAn overview of the various stages of preparation for the administration of OLIMEL N5E is illustrated in Figure 1.

Opening
Remove the protective outer wrapper.
Discard the oxygen absorber bag.
Check the integrity of the pouch and the non-permanent separation membranes. Use only if the
pouch is undamaged, if the non-permanent separation membranes are intact (i.e. there is
no mixing of the contents of the 3 compartments), if the amino acid solution and the
glucose solution are clear, colorless or slightly yellow, and practically free of visible particles,
and if the lipid emulsion is a homogeneous liquid with a milky appearance.
Mixing of the solutions and the emulsion
Ensure that the product is at room temperature when breaking the non-permanent
separation membranes.
Roll the pouch manually from top to bottom (end with loop). The
non-permanent separation membranes will disappear on the side next to the openings. Continue
rolling the pouch until the separation membranes are open for about half their
length.
Mix the pouch by inverting it at least 3 times.
After reconstitution the mixture is a homogeneous emulsion with a milky appearance.
Additives:
The pouch is equipped with sufficient capacity to allow for additives, such as vitamins, electrolytes and
trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening the
non-permanent separation membranes and after mixing the contents of the three
compartments).
Vitamins can also be added to the glucose compartment before the mixture is
reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments).
When making additions to formulations containing electrolytes, the amount of electrolytes already present in the pouch must be considered
Additives must be carried out by qualified personnel under aseptic conditions.
OLIMEL N5E can be supplemented with electrolytes, based on the following table:
Corresponding value for the addition of inorganic phosphate
Including phosphate provided by the lipid emulsion

Trace elements and vitamins:
Stability has been demonstrated with commercially available vitamin and trace element preparations (containing
a maximum of 1 mg of iron).
Compatibility of other additives is available on request.
When making additions, measure the final osmolarity of the mixture before administration into a peripheral vein.
To make an addition:

• the operation must be carried out under aseptic conditions.
• Prepare the injection point of the pouch.
• Puncture the injection point and inject the additives using a needle or a reconstitution device.
• Mix the contents of the pouch and the additives.

Preparation of the infusion
The operation must be carried out under aseptic conditions.
Suspend the pouch.
Remove the plastic protection from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Per 1,000 mL
	Included level	Further maximum addition	o Maximum total level
sodium	35 mmol	115 mmol	150 mmol
potassium	30 mmol	120 mmol	c 150 mmol
magnesium 4.0 mmol 1.6 mmol 5.6 mmol calcium 3.5 mmol 1.5 (0.0(a)) mmol a 5.0 (3.5(a))mmol Inorganic phosphate 0 mmol 3.0 mmol 3.0 mmol Organic phosphate 15 mmol (b) 10 mmol m 25 mmol (b) Administration For single use only. Administer the product only after breaking the non-permanent separation membranes between the 3 compartments and mixing the contents of the 3 compartments. Ensure that the final emulsion for infusion does not show evidence of phase separation. After opening the bag, the contents must be used immediately. Never store the bag open for a subsequent infusion. Do not reconnect any partially used bags. Do not connect the bags in series to avoid the possibility of gaseous embolism due to the gas contained in the main bag. Dispose of any unused product, any derived waste and all necessary devices. Extravasation The catheter site must be checked regularly for possible signs of extravasation. In case of extravasation, administration must be stopped immediately while maintaining the catheter or cannula inserted for immediate patient treatment. If possible, perform aspiration through the inserted catheter or cannula to reduce the amount of liquid present in the tissues before removing the catheter or cannula. Depending on the extravasated product (including one or more products mixed with OLIMEL N5E, if applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken. Treatment options may include non- pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult a plastic surgeon within the first 72 hours. The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once a day. The infusion should not be restarted in the same central vein. Уже начали прием и появились вопросы? Обсудите свое состояние и дальнейшие шаги с врачом онлайн. Поговорить с врачом OLIMEL N7, Emulsion for infusion Read this leaflet carefully before you are given this medicine as it contains important information for you. Keep this leaflet. You may need to read it again. If you have any questions, ask your doctor or nurse. If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4 Contents of this leaflet: 13. What OLIMEL N7 emulsion for infusion is and what it is used for 14. What you need to know before you are given OLIMEL N7 emulsion for infusion 15. How to use OLIMEL N7, emulsion for infusion 16. Possible side effects 17. How to store OLIMEL N7 emulsion for infusion 18. Contents of the pack and other information 1. WHAT IS OLIMEL N7 AND WHAT IS IT USED FOR OLIMEL N7 is an emulsion for infusion. It is presented in the form of a 3-compartment bag. One compartment contains a glucose solution, the second a lipid emulsion and the third an amino acid solution. OLIMEL N7 is used to provide nutrition to adults and children over two years of age via a tube into a vein, when normal oral feeding is not suitable. OLIMEL N7 must be used exclusively under medical supervision. 2. What you need to know before you are given OLIMEL N7 emulsion for infusion OLIMEL N7,emulsion for infusion must not be usedin the following cases In premature newborns, infants and children under 2 years of age If you are hypersensitive (allergic) to egg proteins, soy seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions”section below) or to any of the excipients. If the use of certain amino acids creates problems for your body. -If you have particularly high levels of fats in your blood. -If you suffer from hyperglycemia (too much sugar in the blood). In all cases, the doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of the tests performed. Warnings and precautions Consult your doctor or nurse before you are given OLIMEL N7. If you are given total parenteral nutrition solutions too quickly, this may cause injury or death The infusion must be stopped immediately if you develop signs or symptoms of an allergic reaction (such as, sweating, fever, chills, headache, skin rashes or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soy seeds and egg proteins can cause hypersensitivity reactions. Cross-allergic reactions between soy and peanut proteins have been observed. Olimel N7 contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N7, emulsion for infusion must not be used” above) Difficulty breathing may also be a sign that small particles have formed, which block blood vessels in the lungs (pulmonary vascular precipitates). If you experience breathing difficulties, report it to your doctor or nurse, who will decide what actions to take. Some medicines and illnesses can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. The doctor will carefully monitor you for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may have a higher risk of developing infections from their medical conditions. The use of aseptic (germ-free) techniques during catheter placement, and maintenance, and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk. If you are severely malnourished, to the extent that you receive nutrition intravenously, the doctor must start treatment slowly. In addition, the doctor must carefully monitor you for preventing sudden changes in your fluid levels, vitamins, electrolytes and minerals. The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary. The doctor must be informed in case of: severe kidney problem. You must inform the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment; severe liver problem; blood clotting problem; inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangle-shaped glands located above the kidneys; heart failure; lung disease; accumulation of water in the body (hyperhydration); insufficient water in the body (dehydration); high levels of sugar in the blood (diabetes mellitus) that are untreated; heart attack or stroke secondary to sudden heart failure; severe metabolic acidosis (when the blood is too acidic); generalized infection (septicemia); coma. To verify the effectiveness and overall safety of administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is administered to you for several weeks, your blood will be monitored regularly. The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible undesirable effects. If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, inform your doctor or nurse. The administration will be stopped immediately and restarted in another vein. If your blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N7 or give you a medicine to control your blood sugar level (insulin). OLIMEL N7 can be administered to you via a tube (catheter) only into a large vein in the chest (central vein). Children and adolescents If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used. Other medicines and OLIMEL N7 Tell your doctor if you are taking or have recently taken, or might take or use any other medicine. The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility. OLIMEL N7 must not be administered simultaneously with blood through the same infusion set. Due to the risk of precipitation, OLIMEL N7 must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin The olive oil and soybean oil in OLIMEL N7 contain vitamin K. This vitamin generally does not affect blood-thinning (anticoagulant) drugs, such as coumarin. However, inform your doctor if you are taking anticoagulant drugs. The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids have been eliminated from your blood (which usually are eliminated after a period of 5 or 6 hours without receiving them). Pregnancy, breastfeeding and fertility If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with breast milk, ask your doctor for advice before taking this medicine. OLIMEL N7 can be considered during pregnancy and breastfeeding if necessary Driving and using machines Not relevant 3. How to use OLIMEL N7, emulsion for infusion Dosage OLIMEL N7 must be administered only to adults and children over two years of age. This is an emulsion for infusion, to be administered via a tube (catheter) into a vein. OLIMEL N7 must be at room temperature before use. OLIMEL N7 is for single use only. The infusion of a bag usually lasts between 12 and 24 hours. Dosage - adults The doctor will specify a flow rate corresponding to your needs and clinical condition. The prescription may continue for as long as required, according to your clinical condition. Dosage - children over two years of age and adolescents The doctor will decide the dose and for how long the medicine will be administered. This will depend on age, weight, height, medical conditions and the body's ability to break down and use the components of OLIMEL N7. If you have been given more OLIMEL N7, emulsion for infusion than you should If the dose given is too high or the infusion is too fast, the amino acid content may make your blood too acidic and symptoms of hypervolemia (increased blood volume) may occur. Blood and urine glucose levels may increase and a hyperosmolar syndrome (excessive blood viscosity) may develop and the lipid content may increase triglycerides in your blood. Receiving an infusion that is too fast or an excessively high volume can cause nausea, vomiting, chills, headache, hot flashes, excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be stopped immediately. In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys eliminate the excess product. To prevent such events from happening, the doctor will regularly monitor your condition and test your blood parameters. If you have any doubts about the use of OLIMEL N7, consult your doctor. 4. Possible side effects Like all medicines, this medicine, , may cause side effects, although not everyone will experience them. If you notice any changes in the way you feel, during or after treatment, tell your doctor or nurse promptly. The tests that your doctor will perform while you are taking the medicine reduce the risk of side effects. The infusion will be stopped immediately in case of development of signs or symptoms of an abnormal allergic reaction, such as fever, chills, headache, skin rash or difficulty breathing. With OLIMEL N7 the following side effects have been reported: Frequency-Common: may affect up to 1 in 10 people Fast heart rate (tachycardia). Decreased appetite. Increased blood fat levels (hypertriglyceridemia). Abdominal pain. Diarrhea. Nausea. Increased blood pressure (hypertension). Frequency - Not known: frequency cannot be estimated based on the available data Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site. The following side effects have been reported with similar parenteral nutrition products: Frequency- Very rare: may affect up to 1 in 10,000 people Reduced ability to remove fats (fat overload syndrome) associated with a sudden deterioration in the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after discontinuation of the lipid emulsion infusion: Fever Reduction of red blood cells which can make the skin pale and cause weakness or shortness of breath (anemia). Low white blood cell count, which may increase the risk of infection (leukopenia) Low platelet count, which may increase the risk of bruising and/or bleeding (thrombocytopenia) Coagulation disorders that compromise the blood's ability to clot High levels of fats in the blood (hyperlipidemia) Hepatic lipid infiltration (hepatomegaly) Deterioration of liver function Manifestations involving the central nervous system (e.g., coma). Frequency - Not known: frequency cannot be estimated based on the available data Allergic reactions. Abnormal blood test results for liver function. Problems in the elimination of bile (cholestasis) Increased liver size (hepatomegaly). Jaundice (icterus). Reduced number of platelets (thrombocytopenia). Increased nitrogen levels in the blood (azotemia) Elevated liver enzymes Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress). Reporting of side effects If you experience any side effects, including those not listed in this leaflet, please tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at http://www.agenziafarmaco.gov.it/content/come- segnalare-una-sospetta-reazione-avversa By reporting side effects you can help provide more information on the safety of this medicine. 5. How to store OLIMEL N7, emulsion for infusion Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the container and on the outer packaging (MM/YYYY). The expiry date refers to the last day of the month. Do not freeze. Store in the outer packaging. Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. 6. Contents of the pack and other information What OLIMEL N7, emulsion for infusion contains The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at 11.1%(corresponding to 11.1 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid), an emulsion of lipids at20%(corresponding to 20.0 g/100 mL) (purified olive oil and purified soybean oil) and a solution of glucose at 35%(corresponding to 35.0 g/100 mL) (as glucose monohydrate). The excipients are: Compartment Lipid emulsion Compartment Amino acid solution Compartment Glucose solution Purified egg phospholipid, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections Glacial acetic acid (for pH adjustment), water for injections Hydrochloric acid (for pH adjustment), water for injections Appearance of OLIMEL N7, emulsion for infusion and contents of the packs OLIMEL N7 is an emulsion for infusion packaged in a three-compartment bag. One compartment contains a lipid emulsion, another an amino acid solution and the third a glucose solution. These compartments are separated by non-permanent membranes. Before administration the contents of the compartments must be mixed by rolling the bag on itself from the top until the membranes open. Appearance before reconstitution: The amino acid and glucose solutions are clear, clear colourless or slightly yellow. The lipid emulsion is homogeneous with a milky appearance. Appearance after reconstitution: homogeneous emulsion with a milky appearance The three-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorised additives. To prevent contact with atmospheric oxygen, the bag is packaged in an outer barrier wrapper with oxygen, which contains an oxygen absorber sachet. Packs: 1,000 mL bag: 1 box with 6 bags 1,500 mL bag: 1 box with 4 bags 2,000 mL bag: 1 box with 4 bags 1 bag of 1,000 mL, 1,500 mL and 2,000 mL Not all pack sizes may be marketed. For further information on OLIMEL N7, contact the local representative of the marketing authorisation holder: Marketing Authorisation Holder Baxter S.p.A. Piazzale dell’Industria 20 00144 Rome Italy Manufacturer: Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines Belgium This medicinal product is authorised in the member states of the European economic community with the following names: France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy Denmark, Iceland, Sweden, Norway, Finland, Greece, Cyprus: OLIMEL N7 Austria: Zentro OLIMEL 4,4 % > Germany: Olimel4,4% United Kingdom, Ireland, Malta: Triomel 7g/L nitrogen 1.140 kcal/L  -------------------------------------------------------------------------------------------------------------- The following information is intended exclusively for physicians or healthcare professionals: Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations ATC code: B05 BA10 E.QUALITATIVE AND QUANTITATIVE COMPOSITION OLIMEL N7 is presented as a 3-compartment bag. Each bag contains a glucose solution, a lipid emulsion and an amino acid solution: Content per bag mL 35% Glucose solution (corresponding to 35 g/100 mL) 400 mL 600 mL 800 mL mLmL 11.1% Amino acid solution (corresponding to 11.1 g/100 mL) 400 mL 600 mL 800 mL 20% Lipid emulsion (corresponding to 20 g/100 mL) 200 mL 300 mL 800 mL Composition of the reconstituted emulsion after mixing the contents of the three compartments: Active ingredients1,000 mL1,500 mL2,000 mL Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g Alanine 6.41 g 9.61 g 12.82 g Arginine 4.34 g 6.51 g 8.68 g Aspartic acid 1.28 g 1.92 g 2.56 g Glutamic acid 2.21 g 3.32 g 4.42 g Glycine 3.07 g 4.60 g 6.14 g Histidine 2.64 g 3.97 g 5.29 g Isoleucine 2.21 g 3.32 g 4.42 g Leucine 3.07 g 4.60 g 6.14 g Lysine (equivalent to lysine acetate) 6.97 g (9.75 g) Methionine 2.21 g 3.32 g 4.42 g Phenylalanine 3.07 g 4.60 g 6.14 g Proline 2.64 g 3.97 g 5.29 g Serine 1.75 g 2.62 g 3.50 g Threonine 2.21 g 3.32 g 4.42 g Tryptophan 0.74 g 1.10 g 1.47 g Tyrosine 0.11 g 0.17 g 0.22 g Valine 2.83 g 4.25 g 5.66 g Anhydrous glucose (as Glucose monohydrate) 3.48 g (4.88 g) 5.23 g (7.31 g) 140.00 g (154.00) g 210.00 g (231.00 g) 280.00 g (308.00 g) A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%) corresponding to an essential fatty acids / total fatty acids ratio of 20%. The excipients are: Compartment Lipid emulsion Compartment Amino acid solution Compartment Glucose solution Hydrochloric acid (for pH adjustment), water for injections Nutritional contribution of the reconstituted emulsion for each bag size: Purified egg phospholipid, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections Glacial acetic acid (for pH adjustment), water for injections 1,000 mL a 1,500 mL 2,000 mL Lipids 40 g 60 g 80 g Amino acids 44.3 g F 66.4 g 88.6 g Nitrogen 7.0 g 10.5 g 14.0 g Glucose 140.0 g l 210.0 g 280.0 g Energy: Total calories approx. Non-protein calories approx. Glucose calories Lipid calories approx..(a) Calories non-protein/nitrogen ratio Glucose calories/lipid ratio Lipid calories/total d 1140 kcal 960 kcal 560 kcal a 400 kcal n 137 kcal/g 58/42 35% e 1710 kcal 1440 kcal 840 kcal 600 kcal 137 kcal/g 58/42 35% 2270 kcal 1920 kcal 1120 kcal 800 kcal 137 kcal/g 58/42 35% Electrolytes: i Phosphate( b) l acetate a 3.0 mmol 31 mmol 4.5 mmol 46 mmol 6.0 mmol 62 mmol Approx. pH 6.4 6.4 6.4 a Osmolarity. 1220 mosm/L 1220 mosm/L 1220 mosm/L Includes calories from purified egg phospholipids Phosphate provided by the lipid emulsion B.DOSAGE AND ADMINISTRATION Dosage The use of OLIMEL N7 is not recommended in children under 2 years of age due to the composition and volume being inadequate (see sections 4.4, 5.1 and 5.2 of the SmPC). Do not exceed the maximum daily dose reported below. Due to the static composition of the multi-compartment bag, it may not be possible to simultaneously meet all of the patient's nutritional requirements. Clinical situations may occur in which patients require amounts of nutrients varying from the composition of the static bag. In such a situation, any adjustment of the volume (dose) must take into account the resulting effect that this will have on the dosage of all other nutrients of OLIMEL N7. For example, pediatric patients may have a requirement greater than 0.2 mmol/kg/day of phosphate. In these circumstances, healthcare professionals may consider adjusting the volume (dose) of OLIMEL N7 in order to meet this increased requirement. In adults: The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to metabolize the constituents of OLIMEL N9E, as well as any additional energy or proteins provided orally/enterally, therefore the bag sizes must be chosen accordingly. Average daily requirements are: 0.16-0.35 g nitrogen/kg body weight (1-2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress, 20-40 kcal/kg, 20-40 mL fluids /kg or 1-1.5 mL per kcal spent. For Olimel N7 the maximum daily dose is defined by the total caloric intake, 40 kcal provided in a volume of 35 mL/kg, corresponding to 1.5 g/kg of amino acids, 4.9 g/kg of glucose, and 1.4 g/kg of lipids. For a 70 kg patient this would be equivalent to 2800 mL of OLIMEL N7 per day, which translates to an intake of 108 g of amino acids, 343 g of glucose and 98 g of lipids (i.e. 2352 non-protein kcal and 2793 total kcal). Normally, the flow rate should be increased gradually during the first hour and then adjusted to account for the dose to be administered, the volumes to be taken daily and the duration of the infusion. For OLIMEL N7 the maximum infusion rate is 1.7 mL/kg/hour, corresponding to 0.08 g/kg/hour for amino acids; 0.24 g/kg/hour for glucose and 0.07 g/kg/hour for lipids. In children over two years of age No studies have been conducted in the pediatric population. The dosage depends on energy expenditure, the patient's clinical status and the ability to metabolize the constituents of OLIMEL N7, as well as any additional energy or proteins provided orally/enterally. In addition, daily fluid, nitrogen and energy requirements continuously decrease with age. Two groups were considered, age between 2 and 11 years, and age between 12 and 18 years. For Olimel N7, in the age group between 2 and 11 years, the limiting factors are the phosphate concentration for the daily dose (0.2 mmol/kg/day) and the lipid concentration for the hourly rate. In the age group between 12 and 18 years, the limiting factor is the amino acid concentration for both the daily dose and the hourly rate. The resulting intakes are shown below: g Constituents From 2 to 11 years From 12 to 18 years Recommendeda OLIMEL N7 Max Volume Recommendeda OLIMEL N7 Max Volume A Maximum daily dose Liquids (mL/kg/day) 60 – 120 67 50 – 80 45 Amino acids (g/kg/day) 1 – 2 (up to 3) 2.9 1 – 2 2.0 Glucose (g/kg/day) 12 – 14 (up to 9.3 3 – 10 (up to 14) 6.4 a: Values recommended by the 2005 ESPGHAN/ ESPEN Guidelines Normally, the flow rate should be increased gradually during the first hour and then adjusted taking into account the dose to be administered, the daily volume intake and the duration of the infusion. In general, in small children it is recommended to start the infusion with a low daily dose, and to increase it gradually up to the maximum dosage (see above). Mode and duration of administration For single use only. It is recommended to use the contents immediately after opening the bag and not to store it for a subsequent infusion. After reconstitution, the mixture is homogeneous and has a milky appearance. For instructions on the preparation and handling of the infusion emulsion, see paragraph 6.6. Due to its high osmolarity, OLIMEL N7 can only be administered through a central vein. The recommended infusion duration for a parenteral nutrition bag is between 12 and 24 hours. Treatment with parenteral nutrition can continue for as long as required by the patient's clinical condition. C.INCOMPATIBILITIES Do not add other medicines or other substances to any of the three constituents of the bag or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular the stability of the lipid emulsion). Incompatibilities may arise, for example, from excessive acidity (low pH) or from an unsuitable content of divalent cations (Ca and Mg) which may destabilize the lipid emulsion. As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, can cause the formation of calcium phosphate precipitates. Due to the risk of precipitation, OLIMEL N7 should not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin. Verify compatibility with solutions administered simultaneously through the same infusion set, catheter or cannula. 18) Lipids (g/kg/day) 0.5 - 3 2.7 0.5 - 2 (up to 3) 1.8 Total energy (kcal/kg/day) 60 – 90 76 30 – 75 o 52 Maximum hourly rate OLIMEL N7 (mL/kg/h) 3.3 c 2.7 Amino acids(g/kg/h) 0.20 0.15 0.12 0.12 Glucose (g/kg/h) 1.2 0.46 1.2 a 0.38 Lipids (g/kg/h) 0.13 0.13 0.13 0.11 Do not administer before, simultaneously or after a blood transfusion through the same line, due to the risk of pseudoagglutination. D.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING An overview of the various stages of preparation for the administration of OLIMEL N7 is illustrated in Figure 1. Opening Remove the external protective wrapper. Discard the oxygen absorber bag. Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is not damaged, if the non-permanent separation membranes are intact (i.e. there is no mixing of the contents of the 3 compartments), if the amino acid solution and the glucose solution are clear, colorless or slightly yellow, and practically free of visible particles, and if the lipid emulsion is a homogeneous liquid with a milky appearance. Mixing of the solutions and the emulsion Make sure the product is at room temperature when breaking the non-permanent separation membranes. Roll the bag manually on itself, starting from the top (end with loop). The non-permanent separation membranes will disappear from the side next to the openings. Continue rolling the bag until the separation membranes are open for about half their length. Mix the bag by inverting it at least 3 times. After reconstitution the mixture is a homogeneous emulsion with a milky appearance. Additives: The bag is equipped with sufficient capacity to allow additions, such as vitamins, electrolytes and trace elements. Any addition (including vitamins) must be made to the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments). Vitamins can also be added to the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments). When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag must be considered. Additions must be made by qualified personnel under aseptic conditions. Value corresponding to the addition of inorganic phosphate Including the phosphate provided by the lipid emulsion Trace elements and vitamins: Stability up to the recommended daily dose has been demonstrated. Compatibility of other additives is available on request. When making additions, before administering through a peripheral vein, measure the final osmolarity of the mixture. To make an addition: The operation must be carried out under aseptic conditions. Prepare the injection site of the bag. Puncture the injection site and inject the additives using a syringe or a reconstitution device. Mix the contents of the bag and the additives. Preparation of the infusion The operation must be carried out under aseptic conditions. Suspend the bag. Remove the plastic protection from the administration port. Firmly insert the spike of the infusion set into the administration port. For 1,000 mL Included level Further maximum addition Maximum total level sodium 0 mmol 150 mmol 150 mmol potassium 0 mmol 150 mmol 150 mmol magnesium 0 mmol 5.6 mmol c 5.6 mmol calcium 0 mmol 5.0 (3.5(a)) mmol a 5.0 (3.5a)) mmol Inorganic phosphate 0 mmol 8.0 mmol 8.0 mmol Organic phosphate 3 mmol (b) 22 mmol 25 mmol (b) Administration For single use only. Administer the product only after breaking the non-permanent separation membranes between the 3 compartments and mixing the contents of the 3 compartments. Make sure the final emulsion for infusion shows no evidence of phase separation. After opening the bag, the contents must be used immediately. Never store an open bag for a subsequent infusion. Do not reconnect any partially used bags. Do not connect the bags in series to avoid the possibility of gas embolism due to the gas contained in the main bag. Dispose of any unused product, any waste derived from it and all necessary devices. Extravasation The catheter site must be checked regularly for possible signs of extravasation. In case of extravasation, administration must be stopped immediately while keeping the catheter or cannula inserted for immediate treatment of the patient. If possible, perform an aspiration through the inserted catheter or cannula to reduce the amount of fluid present in the tissues before removing the catheter or cannula. Depending on the extravasated product (including one or more products mixed with OLIMEL N7, if applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken. Treatment options may include non-pharmacological, pharmacological and/or surgical intervention. In case of extensive extravasation, consult a plastic surgeon within the first 72 hours. The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once a day. The infusion should not be restarted in the same central vein. OLIMEL N7E, emulsion for infusion Read this leaflet carefully before you are given this medicine as it contains important information for you. Keep this leaflet. You may need to read it again. If you have any questions, ask your doctor or nurse. If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4. Contents of this leaflet: 19. What OLIMEL N7E emulsion for infusion is and what it is used for 20. What you need to know before you are given OLIMEL N7E emulsion for infusion 21. How to use OLIMEL N7E, emulsion for infusion 22. Possible side effects 23. How to store OLIMEL N7E emulsion for infusion 24. Contents of the pack and other information 1. What is OLIMEL N7E, emulsion for infusion and what is it used for OLIMEL is an emulsion for infusion. It is presented in the form of a 3-compartment bag. One compartment contains a glucose solution with calcium, the second a lipid emulsion and the third a solution of amino acids with other electrolytes. OLIMEL is used to provide nutrition to adults and children over two years of age via a tube into a vein, when normal oral feeding is not suitable. OLIMEL must be used exclusively under medical supervision. 2. What you need to know before you are given OLIMEL N7E, emulsion for infusion OLIMEL N7E, emulsion for infusionmust not be used: In premature newborns, infants and children under 2 years of age If you are hypersensitive (allergic) to egg proteins, soy seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the excipients. If the use of certain amino acids causes problems for your body. If you have particularly high levels of fats in your blood. If you suffer from hyperglycemia (too much sugar in the blood). If you have an abnormally high concentration of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood. In all cases, the doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of the tests performed. Warnings and precautions Consult your doctor or nurse before you are given OLIMEL N7E. If you are given total parenteral nutrition solutions too quickly, this may cause injury or death. The infusion must be stopped immediately if you develop signs or symptoms of an abnormal allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybeans and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soy and peanut proteins have been observed. Olimel N7E contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N7E, emulsion for infusion must not be used” above) Difficulty breathing may also be a sign that small particles have formed, which block blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, tell your doctor or nurse, who will decide what actions to take. The antibiotic called ceftriaxone must not be mixed or administered simultaneously with any solution containing calcium (including OLIMEL N7E) that is administered to you through an intravenous drip. These medicines must not be given to you even through different infusion lines or different infusion sites. However, you may take OLIMEL N7E and ceftriaxone in sequence, one after the other, if infusion lines in different locations are used or if the infusion lines are replaced or thoroughly washed with saline between infusions to avoid the formation of precipitates (calcium-ceftriaxone salt particles). Some drugs and diseases can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. The doctor will monitor you carefully for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may be at increased risk of developing infections from their medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance and during preparation of the nutritional formula (total parenteral nutrition) can reduce this risk. If you are severely malnourished, to the point where you receive nutrition intravenously, the doctor must start treatment slowly. In addition, the doctor must monitor you carefully to prevent sudden changes in your fluid levels, vitamins, electrolytes and minerals. The balance of water and salt in your body and disturbances in metabolism will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary. The doctor must be informed if you have: severe kidney problems. You should tell the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment; severe liver problems; blood clotting problems; inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys; heart failure; lung disease; water accumulation in the body (hyperhydration); insufficient water in the body (dehydration); high levels of sugar in the blood (diabetes mellitus) that are not treated; heart attack or stroke secondary to sudden heart failure; severe metabolic acidosis (when the blood is too acidic); generalized infection (septicemia); coma. To verify the effectiveness and overall safety of administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is given to you for several weeks, your blood will be monitored regularly. The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects). If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, tell your doctor or nurse. Administration will be stopped immediately and restarted in another vein. If your blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N7E or give you a medicine to control your blood sugar level (insulin). OLIMEL N7E can only be given to you through a tube (catheter) into a large vein in the chest (central vein). Children and adolescents If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used. Other medicines and OLIMEL N7E Tell your doctor if you are taking or using, have recently taken or used, or may take or use any other medicine. The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, tell your doctor in advance to verify their compatibility. OLIMEL N7E must not be administered simultaneously with blood through the same infusion set. OLIMEL N7E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tube, because particles may form. If you use the same device to administer these medicines in succession, the device must be thoroughly washed. Due to the risk of precipitation, OLIMEL N7E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin. The olive and soybean oils in OLIMEL N7E contain vitamin K. This vitamin generally does not affect blood-thinning drugs (anticoagulants), such as coumarin. However, tell your doctor if you are taking anticoagulant drugs. The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them). OLIMEL N7E contains potassium. Pay particular attention with patients taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (drugs for treating hypertension) or immunosuppressants. These types of drugs can increase potassium levels in the blood. Pregnancy, breastfeeding and fertility If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding with breast milk, ask your doctor for advice before taking this medicine. OLIMEL N7E may be considered during pregnancy and breastfeeding if necessary Driving and using machines Not relevant 3. How to use OLIMEL N7E, emulsion for infusion Dosage OLIMEL must be administered only in adults and children over two years of age. This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your chest. OLIMEL must be at room temperature before use. OLIMEL N7E is for single use only. The infusion of 1 bag usually lasts from 12 to 24 hours Dosage - adults The doctor will specify a flow rate corresponding to your needs and clinical condition. The prescription may continue for as long as required, according to your clinical condition. Dosage - children over two years of age and adolescents The doctor will decide the dose and for how long the medicine will be administered. This will depend on age, weight, height, medical conditions and the body's ability to break down and use the components of OLIMEL N7E. If you have been given more OLIMEL N7E, emulsion for infusion than you should If the dose given is too high or the infusion is too fast, the amino acid content may make your blood too acidic and symptoms of hypervolemia (increased blood volume) may occur. Blood and urine glucose levels may increase and a hyperosmolar syndrome (excessive blood viscosity) may develop and the lipid content may increase the level of triglycerides in your blood. Receiving an infusion too quickly or too large a volume of OLIMEL N7E can cause nausea, vomiting, chills, headache, hot flashes, excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be stopped immediately. In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys eliminate the excess product. To prevent such events from happening, the doctor will regularly monitor your condition and test your blood parameters. If you have any doubts about the use of this product, please consult your doctor. 4. POSSIBLE SIDE EFFECTS Like all medicines, this medicine can cause side effects, although not everyone will experience them. If you notice any changes in how you feel, during or after treatment, promptly inform your doctor or nurse. The tests your doctor performs while you are taking the medicine reduce the risk of side effects. The infusion will be stopped immediately in the event of the development of signs or symptoms of an allergic reaction, such as sweating, fever, chills, headache, skin rash or difficulty in breathing. With OLIMEL N7E the following side effects have been reported: Frequency-Common: may affect up to 1 in 10 people Fast heart rate (tachycardia). Decreased appetite. Increased levels of fats in the blood (hypertriglyceridemia). Abdominal pain. Diarrhea. Nausea. Increased blood pressure (hypertension). Frequency - Not known: frequency cannot be estimated based on available data Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site. The following side effects have been reported with similar parenteral nutrition products: Frequency- Very rare: may affect up to 1 in 10,000 people Reduced ability to remove lipids (fat overload syndrome) associated with a sudden and rapid deterioration of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the lipid emulsion infusion: Fever Reduced red blood cells, which can make the skin pale and cause weakness or shortness of breath (anemia). Low white blood cell count, which can increase the risk of infection (leukopenia) Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia) Blood clotting disorders that impair the blood's ability to clot High levels of fats in the blood (hyperlipidemia) Fatty infiltration of the liver (hepatomegaly) Worsening of liver function Manifestations affecting the central nervous system (e.g., coma). Frequency- Not known: frequency cannot be estimated based on available data: Allergic reactions. Abnormal blood test results for liver function. Problems with bile drainage (cholestasis) Increased liver size (hepatomegaly). Jaundice (icterus). Reduced number of platelets (thrombocytopenia). Increased nitrogen levels in the blood (azotemia) Elevated liver enzymes Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress). Reporting of side effects If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly through the national reporting system at: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine 5. How to store OLIMEL N7E emulsion for infusion Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the container and on the outer packaging (MM/YYYY). The expiry date refers to the last day of the month. Do not freeze. Store in the outer packaging Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. 6. Package Contents and Other Information What OLIMEL N7E, emulsion for infusion contains The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at 11.1%(corresponding to 11.1 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate, chloride), a lipid emulsion at20%(corresponding to 20 g/100 mL) (purified olive oil and purified soybean oil) and a glucose solution at 35%(corresponding to 35 g/100 mL) (as glucose monohydrate) with calcium. The excipients are: Compartment Lipid emulsion Compartment Amino acid solution Compartment Glucose solution Purified egg phospholipid, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections Glacial acetic acid (for pH adjustment), water for injections Hydrochloric acid (for pH adjustment), water for injections Appearance of OLIMEL N7E, emulsion for infusion and contents of the pack OLIMEL N7E is an emulsion for infusion packaged in a three-compartment bag. One compartment contains a lipid emulsion, another compartment an amino acid solution with electrolytes and the third compartment a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration the contents of the compartments must be mixed by rolling the bag on itself starting from the top until the membranes open. Appearance before reconstitution: The amino acid and glucose solutions are clear, clear colourless or slightly yellow. The lipid emulsion is homogeneous with a milky appearance. Appearance after reconstitution: homogeneous emulsion with a milky appearance The 3-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorised additives. To prevent contact with atmospheric oxygen, the bag is packaged in an outer barrier packaging with oxygen barrier, which contains an oxygen absorber sachet. Pack sizes: 1,000 mL bag: 1 box with 6 bags 1,500 mL bag: 1 box with 4 bags 2,000 mL bag: 1 box with 4 bags 1 bag of 1,000 mL, 1,500 mL and 2,000 mL Not all pack sizes may be marketed. Marketing Authorisation Holder Baxter S.p.A. Piazzale dell’Industria 20 00144 Rome Italy Manufacturer: Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines Belgium This medicinal product is authorised in the member states of the European economic community with the following names: France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden, Norway, Finland, Greece, Cyprus : OLIMEL N7E Austria: ZentroOLIMEL 4,4 % mit Elektrolyten > Germany: Olimel 4,4% E United Kingdom, Ireland, Malta: Triomel 7g/L nitrogen 1140 kcal/L with electrolytes Hungary: Olimel 7 g/L nitrogén elektrolitokkal emulziós infúzió  -------------------------------------------------------------------------------------------------------------- The following information is intended exclusively for physicians or healthcare professionals: Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations ATC code: B05 BA10 F.QUALITATIVE AND QUANTITATIVE COMPOSITION OLIMEL N7E is presented as a 3-compartment bag. Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with other electrolytes: Content per bag 1,000 mL 1,500 mL 2,000 mL 35% Glucose solution (corresponding to 35 g/100 mL) 400 mL 600 mL 800 mL 11.1% Amino acid solution (corresponding to 11.1 g/100 mL) 400 mL 600 mL 800 mL 20% Lipid emulsion (corresponding to 20 g/100 mL) 200 mL 300 mL 400 mL Composition of the reconstituted emulsion after mixing the contents of the three compartments: Active ingredients1,000 mL1,500 mL2,000 mL Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g Alanine 6.41 g 9.61 g 12.82 g Arginine 4.34 g 6.51 g 8.68 g Aspartic acid 1.28 g 1.92 g 2.56 g Glutamic acid 2.21 g 3.32 g 4.42 g Glycine 3.07 g 4.60 g 6.14 g Histidine 2.64 g 3.97 g 5.29 g Isoleucine 2.21 g 3.32 g 4.42 g Leucine 3.07 g 4.60 g 6.14 g Lysine (equivalent to lysine acetate) 6.97 g (9.75g) Methionine 2.21 g 3.32 g 4.42 g Phenylalanine 3.07 g 4.60 g 6.14 g Proline 2.64 g 3.97 g 5.29 g Serine 1.75 g 2.62 g 3.50 g Threonine 2.21 g 3.32 g 4.42 g Tryptophan 0.74 g 1.10 g 1.47 g Tyrosine 0.11 g 0.17 g 0.22 g Valine 2.83 g 4.25 g 5.66 g Sodium acetate, trihydrate 1.50 g 2.24 g 2.99 g Sodium glycerophosphate hydrate 3.67 g 5.51 g 7.34 g Potassium chloride 2.24 g 3.35 g 4.47 g Magnesium chloride, hexahydrate 0.81 g 1.22 g 1.62 g Calcium chloride, dihydrate 0.52 g 0.77 g 1.03 g Anhydrous glucose (equivalent to Glucose monohydrate) 3.48 g (4.88 g) 5.23 g (7.31 g) 140.00 g (154.00 g) 210.00 g (231.00 g) 280.00 g (308.00 g) A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%) corresponding to an essential fatty acids / total fatty acids ratio of 20%. Gli eccipienti sono: Compartimento Emulsione di lipidi Compartimento Soluzione di amminoacidi Compartimento Soluzione di glucosio Acido cloridrico (per l’aggiustamento del pH), acqua per preparazioni iniettabili Apporto nutritivo della emulsione ricostituita per ciascun formato della sacca: Fosfatide purificato di uovo, glicerolo, sodio oleato, sodio idrossido (per l’aggiustamento del pH), acqua per preparazioni iniettabili Acido acetico glaciale (per l’aggiustamento del pH), acqua per preparazioni iniettabili n 1.000 mL 1.500 mL 2.000 mL e Lipidi 40 g 60 g 80 g Amminoacidi 44,3 g 66,4 g 88,6 g g Azoto 7,0 g 10,5 g 14,0 g Glucosio 140,0 g 210,0 g 280,0 g A Energia: Calorie totali appross. Calorie non proteiche. Calorie glucosio Calorie lipidiche.(a) 1.140 kcal 960 kcal 560 kcal 400 kcal 1.710 kcal 1.440 kcal 840 kcal 600 kcal 2.270 kcal 1.920 kcal 1.120 kcal 800 kcal Include calorie da fosfatidi purificati di uovo Include fosfato fornito dall'emulsione di lipidi G.POSOLOGIA E MODO DI SOMMINISTRAZIONEPosologia L’uso di OLIMEL N7E non è raccomandato nei bambini al di sotto di 2 anni a causa della composizione e del volume non adeguati (vedere paragrafi 4.4, 5.1 e 5.2 dell’RCP). Non superare la dose massima giornaliera riportata di seguito. A causa della composizione statica della sacca a compartimenti multipli, può non essere possibile riuscire a soddisfare simultaneamente tutti i fabbisogni nutritivi del paziente. Possono verificarsi situazioni cliniche in cui i pazienti richiedano quantità di elementi nutritivi variabili rispetto alla composizione della sacca statica. In tale situazione, qualunque aggiustamento del volume (dose) deve prendere in considerazione l'effetto risultante che ciò avrà sul dosaggio di tutti gli altri elementi nutritivi di OLIMEL N7E. Ad esempio, i pazienti pediatrici possono avere un fabbisogno superiore a 0,2 mmol/kg/giorno di fosfato. In queste circostanze, gli operatori sanitari possono prendere in considerazione l'aggiustamento del volume (dose) di OLIMEL N7E al fine di soddisfare tale fabbisogno aumentato. Negli adulti: Il dosaggio dipende dal dispendio di energie, dallo stato clinico, dal peso corporeo e dalla capacità di metabolizzare i costituenti di OLIMEL N7E del paziente, oltre che dall’energia o dalle proteine ulteriori fornite oralmente/enteralmente, pertanto i formati della sacca devono essere scelti di conseguenza. I requisiti medi giornalieri sono: 0,16-0,35 g azoto/kg peso corporeo (1-2 g di amminoacidi/kg), secondo lo stato nutrizionale del paziente e il grado di stress catabolico, 20-40 kcal/kg, 20-40 mL fluidi /kg o 1-1,5 mL per kcal spese. Per Olimel N7E la dose quotidiana massima è definita dall'apporto totale calorico, 40 kcal fornite in un volume di 35 mL/kg, corrispondenti a 1,5g/kg amminoacidi, 4,9 g/kg glucosio, e 1,4 g/kg lipidi,1,2 mmol/kg sodio e 1,1 mmol/kg potassio. Per un paziente di 70 kg questo sarebbe equivalente a 2450 mL di OLIMEL N7E al giorno, che si traduce in un apporto di 108g amminoacidi, 343 g glucosio e 98 g lipidi (cioè 2352 kcal non proteiche e 2793 kcal totali). Rapporto calorie non proteiche/azoto Rapporto calorie glucosio/lipidi Calorie lipidi/totali 137 kcal/g 58/42 35% 137 kcal/g 58/42 35% 137 kcal/g o 58/42 35% Elettroliti: sodio potassio magnesio calcio Fosfato (b) acetato cloruro 35,0 mmol 30,0 mmol 4,0 mmol 3,5 mmol 15,0 mmol 45 mmol 45 mmol 52,5 mmol 45,0 mmol m 6,0 mmol 5,3 mmol r 67 mmol 68 mmol c 70,0 mmol a 60,0 mmol 8,0 mmol 7,0 mmol 30,0 mmol 89 mmol 90 mmol pH. 6,4 6,4 6,4 Osmolarità. 1.360 mosm/L a 1.360 mosm/L 1.360 mosm/L Normalmente, la velocità del flusso deve essere aumentata gradualmente durante la prima ora quindi deve essere regolata per tener conto della dose da somministrare, i volumi da assumere quotidianamente e la durata dell'infusione. Per OLIMEL N7E la velocità d'infusione massima è 1,7 mL/kg/ora, corrispondenti a 0,08 g/kg/ora amminoacidi, 0,24 g/kg/ora glucosio e 0,07 g/kg/ora lipidi. Nei bambini di età superiore a due anni Non esistono studi eseguiti sulla popolazione pediatrica. Il dosaggio dipende dal dispendio di energie, dallo stato clinico, dal peso corporeo e dalla capacità di metabolizzare i costituenti di OLIMEL N7E del paziente, oltre che da energia o proteine ulteriori fornite oralmente/enteralmente, pertanto, i formati della sacca devono essere scelti di conseguenza. Inoltre, le esigenze quotidiane di liquidi, azoto ed energia si riducono continuamente con l'età. Sono stati presi in considerazione 2 gruppi, età tra 2 e 11 anni, ed età tra 12 e 18 anni. Per Olimel N7E, nel gruppo di età tra 2 e 11 anni i fattori limitanti sono la concentrazione dei fosfati per la dose giornaliera (0,2 mmol/kg/die)a e la concentrazione dei lipidi per la velocità oraria. Nel gruppo di età tra 12 e 18 anni i fattori limitanti sono la concentrazione dei fosfati per la dose giornaliera (0,2 mmol/kg/die)a e la concentrazione degli amminoacidi per la velocità oraria. Gli apporti risultanti sono mostrati di seguito: Costituenti Da 2 a 11 anni Da 12 a 18 anni Raccomandatoa a n OLIMEL N7E Vol Massimo Raccomandatoa OLIMEL N7E Vol Massimo Dose massima giornaliera Liquidi (mL/kg/d) 60 – 120 a 13 50 – 80 13 Amminoacidi (g/kg/d) 1 – 2 (fino a 3) 0,6 1 – 2 0,6 Glucosio (g/kg/d) i l 12 – 14 (fino a 18) 1,9 3 – 10 (fino a 14) 1,9 Lipidi (g/kg/d) a 0,5 - 3 0,5 0.5 - 2 (fino a 3) 0,5 Energia totale (kcal/kg/d) t 60 – 90 15 30 – 75 15 I Massima velocità all’ora OLIMEL N7E (mL/kg/h) 3,3 2,7 Amino acidi(g/kg/h) a 0,20 0,15 0,12 0,12 Glucosio (g/kg/h) i 1,2 0,46 1,2 0,38 z Lipidi (g/kg/h) 0,13 0,13 0,13 0,11 a: Valori raccomandati dalla Linee Guida 2005 ESPGHAN/ ESPEN Normalmente, la velocità del flusso si deve aumentare gradualmente durante la prima ora e poi deve essere regolata prendendo in considerazione la dose da somministrare, l’apporto di volume giornaliero e la durata dell’infusione In generale, nei bambini piccoli si raccomanda di iniziare l'infusione con una dose giornaliera bassa, e di aumentarla gradualmente fino al dosaggio massimo (vedere sopra). Modo e durata di somministrazione Solo per uso singolo. Si raccomanda di usare il contenuto immediatamente dopo l’apertura della sacca e di non conservarlo per un’infusione successiva. . Dopo la ricostituzione, la miscela è omogenea e ha un aspetto lattiginoso. Per istruzioni sulla preparazione e la manipolazione dell'emulsione per infusione, vedere il paragrafo 6.6. Per la sua alta osmolarità, OLIMEL N7E può essere somministrato solo attraverso una vena centrale. La durata d'infusione raccomandata per una sacca per nutrizione parenterale è compresa tra 12 e 24 ore. Il trattamento con nutrizione parenterale può proseguire per tutto il tempo richiesto dalle condizioni cliniche del paziente. F.INCOMPATIBILITÀNon aggiungere altro medicinale o altre sostanze a uno qualsiasi dei costituenti della sacca o all'emulsione ricostituita senza averne prima verificato la compatibilità e la stabilità della preparazione risultante (in particolare la stabilità dell'emulsione lipidica). Le incompatibilità possono derivare, ad esempio, da eccessiva acidità (pH basso) o da contenuto non idoneo di cationi bivalenti (Ca e Mg ) che possono destabilizzare l'emulsione di lipidi. Come con qualsiasi altra miscela per la nutrizione parenterale, è necessario prendere in considerazione il rapporto calcio/fosfato. Un’eccessiva aggiunta di calcio e fosfato, in particolar modo sotto forma di sali minerali, può causare la formazione di precipitati di fosfato di calcio. OLIMEL N7E contiene ioni calcio che rappresentano un rischio ulteriore di coagulazione nel sangue o in emocomponenti anticoagulati o conservati con citrato. Il ceftriaxone non deve essere miscelato o somministrato in concomitanza con soluzioni endovenose contenenti calcio, compreso OLIMEL N7E, attraverso la stessa linea di infusione (per es., tramite un connettore a Y) a causa del rischio di precipitazione del sale di ceftriaxone-calcio (vedere paragrafi 4.4 e 4.5 dell’RCP). Il ceftriaxone e le soluzioni contenenti calcio possono essere somministrati in sequenza uno dopo l'altro se si utilizzano linee di infusione in diverse sedi o se le linee di infusione vengono sostituite o sono state accuratamente lavate con soluzione fisiologica tra un'infusione e l'altra per evitare la formazione di precipitati. A causa del rischio di precipitazione, OLIMEL N7E non deve essere somministrato attraverso la stessa linea di infusione o mescolato con l’antibiotico ampicillina o l’antiepilettico fosfenitoina. Verificare la compatibilità con le soluzioni somministrate contemporaneamente attraverso lo stesso set di somministrazione, catetere o cannula. Non somministrare prima, contemporaneamente o dopo una emotrasfusione tramite la stessa linea, a causa del rischio di pseudoagglutinazione. F.PRECAUZIONI PARTICOLARI PER LO SMALTIMENTO E LA MANIPOLAZIONE Una visione di insieme degli vari stadi di preparazione per la somministrazione di OLIMEL N7E viene illustrata nella Figura 1 . Apertura Rimuovere l'involucro esterno di protezione. Gettare il sacchetto dell'assorbitore di ossigeno. Verificare l'integrità della sacca e delle membrane di separazione non permanenti. Usare solo se la sacca non è danneggiata, se le membrane di separazione non permanenti sono intatte (cioè non è presente miscelazione del contenuto dei 3 compartimenti), se la soluzione di amminoacidi e la soluzione di glucosio sono limpide, incolori o lievemente gialle, ed in pratica prive di particelle visibili, e se l'emulsione di lipidi è un liquido omogeneo con aspetto lattiginoso. Miscelazione delle soluzioni e dell'emulsione Accertarsi che il prodotto sia a temperatura ambiente quando si rompono le membrane di separazione non permanenti. Arrotolare manualmente la sacca su se stessa, partendo dalla parte alta (estremità con cappio). Le membrane di separazione non permanenti scompariranno dal lato accanto alle aperture. Continuare ad arrotolare la sacca finché le membrane di separazione non siano aperte per circa metà della loro lunghezza. Mescolare la sacca capovolgendola almeno 3 volte. Dopo la ricostituzione la miscela è una emulsione omogenea di aspetto lattiginoso. Aggiunte: La sacca è dotata di una capacità sufficiente a consentire aggiunte, quali vitamine, elettroliti ed elementi in tracce. Un'eventuale aggiunta (incluse le vitamine) va fatta nella miscela ricostituita (dopo l'apertura delle membrane di separazione non permanenti e dopo la miscelazione del contenuto dei tre compartimenti). È possibile aggiungere vitamine anche nel compartimento del glucosio prima che la miscela sia ricostituita (prima dell'apertura delle membrane di separazione non permanenti e prima della miscelazione dei tre compartimenti). Quando si eseguono le aggiunte alle formulazioni contenenti elettroliti, si deve considerare la quantità di elettroliti già presente nella sacca Le aggiunte devono essere effettuate da personale qualificato in condizioni asettiche. OLIMEL N7E si può integrare con elettroliti, sulla base della tabella seguente: e Per 1.000 mL g Livello incluso Aggiunta ulteriore massima Livello totale massimo sodio 35 mmol 115 mmol 150 mmol potassio 30 mmol 120 mmol 150 mmol A magnesio 4,0 mmol 1,6 mmol 5,6 mmol calcio 3,5 mmol 1,5 (0,0(a)) mmol 5,0 (3,5(a)) mmol Fosfato inorganico 0 mmol 3,0 mmol 3,0 mmol Fosfato organico 15 mmol (b) 10 mmol 25 mmol (b) Valore corrispondente all'aggiunta del fosfato inorganico Incluso il fosfato fornito dall'emulsione di lipidi Elementi in tracce e vitamine: La stabilità è stata dimostrata con preparazioni di vitamine e oligoelementi in commercio (contenenti al massimo 1 mg di ferro). La compatibilità di altri additivi è disponibile su richiesta. When making additions, before peripheral vein administration, measure the final osmolarity of the mixture. To make an addition: The operation must take place under aseptic conditions. Prepare the injection point of the bag. Puncture the injection point and inject the additives using an injection needle or a reconstitution device. Mix the contents of the bag and the additions. Preparation of the infusion The operation must take place under aseptic conditions. Suspend the bag. Remove the plastic protection from the administration point. Firmly insert the spike of the infusion set into the administration point. 1 2 3 4 5 6 Administration For single use only. Administer the product only after breaking the non-permanent separation membranes between the 3 compartments and mixing the contents of the 3 compartments. Ensure that the final emulsion for infusion does not show evidence of phase separation. After opening the bag, the contents must be used immediately. Never store the bag open for a subsequent infusion. Do not reconnect any partially used bags. Do not connect the bags in series to avoid the possibility of gas embolism due to gas contained in the main bag. Dispose of any unused product, any derived waste and all necessary devices. Extravasation The catheter site must be checked regularly for possible signs of extravasation. In case of extravasation, administration must be stopped immediately while maintaining the catheter or cannula inserted for immediate patient treatment. If possible, perform an aspiration through the inserted catheter or cannula to reduce the amount of liquid present in the tissues before removing the catheter or cannula. Depending on the extravasated product (including one or more products mixed with OLIMEL N7E, if applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken. Treatment options may include non- pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult a plastic surgeon within the first 72 hours. The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once a day. The infusion should not be restarted in the same central vein. OLIMEL N9, emulsion for infusion Read this leaflet carefully before you are given this medicine as it contains important information for you. Keep this leaflet. You may need to read it again. If you have any questions, ask your doctor or nurse. If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4 Contents of this leaflet: 25. What OLIMEL N9 emulsion for infusion is and what it is used for 26. What you need to know before you are given OLIMEL N9 emulsion for infusion 27. How to use OLIMEL N9, emulsion for infusion 28. Possible side effects 29. How to store OLIMEL N9 emulsion for infusion 30. Contents of the pack and other information 1. What is OLIMEL N9 emulsion for infusion and what is it used for OLIMEL N9 is an emulsion for infusion. It is presented in the form of a 3-compartment bag. One compartment contains a glucose solution, the second a lipid emulsion and the third an amino acid solution. OLIMEL N9 is used to provide nutrition to adults and children over two years of age via a tube into a vein, when normal oral feeding is not suitable. OLIMEL N9 must be used exclusively under medical supervision. 2. What you need to know before you are given OLIMEL N9 emulsion for infusion OLIMEL N9 emulsion for infusion must not be used in the following cases In premature newborns, infants and children under 2 years of age If you are hypersensitive (allergic) to egg proteins, soybean seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the excipients. If the use of certain amino acids causes problems for your body. If you have particularly high levels of fats in your blood. If you suffer from hyperglycemia (too much sugar in the blood). In all cases, the doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of the tests performed. Warnings and precautions Consult your doctor or nurse before you are given OLIMEL N9. If you are given total parenteral nutrition solutions too quickly, this can cause injury or death. The infusion must be stopped immediately if you develop signs or symptoms of allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybean and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soy and peanut proteins have been observed. Olimel N9 contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or corn-derived products (see section “OLIMEL N9, emulsion for infusion must not be used” above) Difficulty breathing may also be a sign that small particles have formed, which block blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, report it to your doctor or nurse, who will decide what actions to take. Some medications and illnesses can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. The doctor will monitor you carefully for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may have a higher risk of developing infections from their medical conditions. The use of aseptic (germ-free) techniques during catheter placement, and maintenance of the catheter and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk. If you are severely malnourished, to the extent that you receive nutrition intravenously, the doctor must start treatment slowly. In addition, the doctor must monitor you carefully to prevent sudden changes in your fluid, vitamin, electrolyte and mineral levels. The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary. The doctor must be informed in case of: severe kidney problems. You must inform the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment; severe liver problems; blood clotting problems; inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangular-shaped glands located above the kidneys; heart failure; lung disease; accumulation of water in the body (hyperhydration); insufficient water in the body (dehydration); high levels of sugar in the blood (diabetes mellitus) that are not treated; heart attack or stroke secondary to sudden heart failure; severe metabolic acidosis (when the blood is too acidic); generalized infection (septicemia); coma. To verify the effectiveness and overall safety of administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is administered to you for several weeks, your blood will be monitored regularly. The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects). If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, inform your doctor or nurse. The administration will be stopped immediately and restarted in another vein. If the blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N9 or give you a medicine to control blood sugar levels (insulin). OLIMEL N9 can be administered to you via a tube (catheter) into a large vein in the chest (central vein). Children and adolescents If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used. Other medicines and OLIMEL N9 Tell your doctor if you are taking or using, have recently taken or used, or might take or use any other medicine. The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility. OLIMEL N9 must not be administered simultaneously with blood through the same infusion set. Due to the risk of precipitation, OLIMEL N9 must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin. The olive and soybean oils in OLIMEL N9 contain vitamin K. This vitamin generally does not affect blood-thinning medications (anticoagulants), such as coumarin. However, inform your doctor if you are taking anticoagulant medications. The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them). Pregnancy, breastfeeding and fertility If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor for advice before taking this medicine. OLIMEL N9 can be considered during pregnancy and breastfeeding if necessary Driving and using machines Not relevant 3. How to use OLIMEL N9 emulsion for infusion Dosage OLIMEL must be administered only to adults and children over two years of age. This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your chest. OLIMEL must be at room temperature before use. OLIMEL N9 is for single use only. The infusion of 1 bag usually lasts from 12 to 24 hours. Dosage - adults The doctor will specify a flow rate corresponding to your needs and clinical condition. The prescription may continue for as long as required, according to your clinical condition. Dosage - children over two years of age and adolescents The doctor will decide the dose and for how long the medicine will be administered. This will depend on age, weight, height, medical conditions and the body's ability to break down and use the components of OLIMEL N9. If you have been given more OLIMEL N9, emulsion for infusion than you should If the dose given is too high or the infusion is too fast, the amino acid content may make your blood too acidic and symptoms of hypervolemia (increased circulating blood volume) may occur. Blood and urine glucose levels may increase and a hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase the level of triglycerides in your blood. Receiving an infusion too quickly or too large a volume of OLIMEL N9 can cause nausea, vomiting, chills, headache, hot flashes, excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be stopped immediately. In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys eliminate excess product. To prevent such events from happening, the doctor will regularly monitor your condition and test your blood parameters. If you have any doubts about the use of OLIMEL N9, consult your doctor. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everyone gets them. If you notice any changes in how you feel during or after treatment, tell your doctor or nurse promptly. The tests your doctor will perform while you are taking the medicine reduce the risk of side effects. The infusion will be stopped immediately in case of development of signs or symptoms of an abnormal allergic reaction, such as fever, chills, headache, skin rash or difficulty breathing. With OLIMEL N9 the following side effects have been reported: Frequency-Common: may affect up to 1 in 10 people: Fast heart rate (tachycardia). Decreased appetite. Increased levels of fats in the blood (hypertriglyceridemia). Abdominal pain. Diarrhea. Nausea. Increased blood pressure (hypertension). Frequency - Not known: frequency cannot be estimated based on the available data Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters / vesicles, inflammation, thickening or constriction of the skin at the infusion site The following side effects have been reported with similar parenteral nutrition products: Frequency- Very rare: may affect up to 1 in 10,000 people Reduced ability to remove fats (fat overload syndrome) associated with a sudden and abrupt deterioration of the patient's medical condition. The following signs of fat overload syndrome are usually reversible after stopping the infusion of the lipid emulsion: Fever Reduced red blood cells which can make the skin pale and cause weakness or shortness of breath (anemia). Low white blood cell count, which can increase the risk of infection (leukopenia) Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia) Blood clotting disorders that impair the blood's ability to clot High levels of fats in the blood (hyperlipidemia) Hepatic lipid infiltration (hepatomegaly) Worsening of liver function Manifestations affecting the central nervous system (e.g., coma). Frequency Not known: frequency cannot be estimated based on the available data Allergic reactions. Abnormal blood test results for liver function. Problems with bile excretion (cholestasis) Increased liver size (hepatomegaly). Jaundice (icterus). Reduced number of platelets (thrombocytopenia). Increased levels of nitrogen in the blood (azotemia). Elevated liver enzymes Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress). Reporting of side effects If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at: http://www.agenziafarmaco.gov.it/content/come- segnalare-una-sospetta-reazione-avversa. By reporting side effects you can help provide more information on the safety of this medicine 5. How to store OLIMEL N9, emulsion for infusion Keep this medicine out of sight and reach of children. Do not use this medicine after the expiry date which is stated on the container and on the outer packaging (MM/YYYY). The expiry date refers to the last day of the month. Do not freeze. Store in the outer packaging. Do not dispose of any medicine in drain water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. 6. Contents of the pack and other information What OLIMEL N9, emulsion for infusion contains The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at 14.2%(corresponding to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid), a lipid emulsion at 20%(corresponding to 20.0 g/100 mL) (purified olive oil and purified soybean oil) and a glucose solution at 27.5%(corresponding to 27.5 g/100 mL) (as glucose monohydrate). The excipients are: CompartmentCompartmentCompartment Lipid emulsionAmino acid solutionGlucose solution Purified egg phospholipid, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections Glacial acetic acid (for pH adjustment), water for injections Hydrochloric acid (for pH adjustment), water for injections Appearance of OLIMEL N9, emulsion for infusion and contents of the pack OLIMEL N9 is an emulsion for infusion packaged in a three-compartment bag. One compartment contains a lipid emulsion, another compartment an amino acid solution with electrolytes and the third compartment a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration, the contents of the compartments must be mixed by rolling the bag on itself starting from the top until the membranes open. Appearance before reconstitution: The amino acid and glucose solutions are clear, clear colorless or slightly yellow. The lipid emulsion is homogeneous with a milky appearance. Appearance after reconstitution: homogeneous emulsion with a milky appearance The 3-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorized additives. To prevent contact with air oxygen, the bag is packaged in an outer barrier wrapper for oxygen, which contains an oxygen absorber bag. Pack sizes: 1,000 mL bag: 1 box with 6 bags 1,500 mL bag: 1 box with 4 bags 2,000 mL bag: 1 box with 4 bags 1 bag of 1,000 mL, 1,500 mL and 2,000 mL. Not all pack sizes may be marketed. Marketing Authorisation Holder Baxter S.p.A. Piazzale dell’Industria 20 00144 Rome Italy Manufacturer: Baxter S.A., Boulevard René Branquart, 80, 7860 Lessines Belgium This medicinal product is authorised in the member states of the European Economic Community with the following names: France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden, Norway, Finland, Greece, Cyprus: OLIMEL N9 Austria: ZentroOLIMEL 5,7 % > Germany: Olimel 5,7% United Kingdom, Ireland, Malta: Triomel 9g/L nitrogen 1070 kcal/L Hungary: Olimel 9 g/L nitrogén emulziós infúzió  -------------------------------------------------------------------------------------------------------------- The following information is intended exclusively for physicians or healthcare professionals: Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations ATC code: B05 BA10 H.QUALITATIVE AND QUANTITATIVE COMPOSITIONOLIMEL N9 is presented as a 3-compartment bag. Each bag contains a glucose solution, a lipid emulsion and an amino acid solution: Content per bag 1,000 mL 1,500 mL 2,000 mL 27.5% Glucose solution (corresponding to 27.5 g/100 mL) 400 mL 600 mL 800 mL 14.2% Amino acid solution 400 mL 600 mL 800 mL (corresponding to 14.2 g/100 mL) 20% Lipid emulsion (corresponding to 20 g/100 mL) 200 mL 300 mL 400 mL Composition of the reconstituted emulsion after mixing the contents of the three compartments: Active ingredients1,000 mL1,500 mL2,000 mL Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g Alanine 8.24 g 12.36 g 16.48 g Arginine 5.58 g 8.37 g 11.16 g Aspartic acid 1.65 g 2.47 g 3.30 g Glutamic acid 2.84 g 4.27 g 5.69 g Glycine 3.95 g 5.92 g 7.90 g Histidine 3.40 g 5.09 g 6.79 g Isoleucine 2.84 g 4.27 g 5.69 g Leucine 3.95 g 5.92 g 7.90 g Lysine (equivalent to lysine acetate) 8.96 g (12.64 g) Methionine 2.84 g 4.27 g 5.69 g Phenylalanine 3.95 g 5.92 g 7.90 g Proline 3.40 g 5.09 g 6.79 g Serine 2.25 g 3.37 g 4.50 g Threonine 2.84 g 4.27 g 5.69 g Tryptophan 0.95 g 1.42 g 1.90 g Tyrosine 0.15 g 0.22 g 0.30 g Valine 3.64 g 5.47 g 7.29 g Anhydrous glucose (as glucose monohydrate) 4.48 g (6.32 g) 6.72 g (9.48 g) 110.00 g (121.00 g) 165.00 g (181.50 g) 220.00 g (242.00 g) Gli eccipienti sono: Compartimento Emulsione di lipidi Compartimento Soluzione di amminoacidi Compartimento Soluzione di glucosio Fosfatide purificato di uovo, glicerolo, sodio oleato, sodio idrossido (per l’aggiustamento del pH), acqua per preparazioni iniettabili Acido acetico glaciale (per l’aggiustamento del pH), acqua per preparazioni iniettabili Acido cloridrico (per l’aggiustamento del pH), acqua per preparazioni iniettabili Apporto nutritivo della emulsione ricostituita per ciascun formato della sacca: 1.000 mL 1.500 mL 2.000 mL g Lipidi 40 g 60 g 80 g Amminoacidi 56,9 g 85,4 g 113,9 g A Azoto 9,0 g 13,5 g 18,0 g Glucosio 110,0 g 165,0 g 220,0 g Energia: Calorie totali appross. 1070 kcal 1600 kcal 2140 kcal Include calorie da fosfatidi purificati di uovo Include fosfato fornito dall'emulsione di lipidi C.POSOLOGIA E MODO DI SOMMINISTRAZIONEPosologia L’uso di OLIMEL N9 non è raccomandato nei bambini al di sotto di 2 anni a causa della composizione e del volume non adeguati (vedere paragrafi 4.4, 5.1 e 5.2 dell’RCP). Non superare la dose massima giornaliera riportata di seguito. A causa della composizione statica della sacca a compartimenti multipli, può non essere possibile riuscire a soddisfare simultaneamente tutti i fabbisogni nutritivi del paziente. Possono verificarsi situazioni cliniche in cui i pazienti richiedano quantità di elementi nutritivi variabili rispetto alla composizione della sacca statica. In tale situazione, qualunque aggiustamento del volume (dose) deve prendere in considerazione l'effetto risultante che ciò avrà sul dosaggio di tutti gli altri elementi nutritivi di OLIMEL N9. Ad esempio, i pazienti pediatrici possono avere un fabbisogno superiore a 0,2 mmol/kg/giorno di fosfato. In queste circostanze, gli operatori sanitari possono prendere in considerazione l'aggiustamento del volume (dose) di OLIMEL N9 al fine di soddisfare tale fabbisogno aumentato. Negli adulti: Il dosaggio dipende dal dispendio di energie, dallo stato clinico, dal peso corporeo e dalla capacità di metabolizzare i costituenti di OLIMEL N9 del paziente, oltre che dall’energia o dalle proteine ulteriori fornite oralmente/enteralmente, pertanto i formati della sacca devono essere scelti di conseguenza. I requisiti medi giornalieri sono: 0,16-0,35 g azoto/kg peso corporeo (1-2 g di amminoacidi/kg), secondo lo stato nutrizionale del paziente e il grado di stress catabolico, 20-40 kcal/kg, 20-40 mL fluidi /kg o 1-1,5 mL per kcal spese. Per OLIMEL N9 la dose quotidiana massima è definita dall'apporto fluidi degli amminoacidi, 35 mL/kg, corrispondenti a 2,0 g/kg amminoacidi, 3,9 g/kg glucosio e 1,4 g/kg lipidi. Per un paziente di 70 kg questo sarebbe equivalente a 2450 mL di OLIMEL N9 al giorno, che si traduce in un apporto di 140 g amminoacidi, 270 g glucosio e 98 g lipidi, (cioè 2058 kcal non proteiche e 2622 kcal totali). Normalmente, la velocità del flusso deve essere aumentata gradualmente durante la prima ora quindi deve essere regolata per tener conto della dose da somministrare, i volumi da assumere quotidianamente e la durata dell'infusione. Calorie non proteiche. Calorie glucosio Calorie lipidiche..(a) Rapporto calorie non proteiche/azoto Rapporto calorie glucosio/lipidi Calorie lipidi/totali 840 kcal 440 kcal 400 kcal 93 kcal/g 52/48 37% 1260 kcal 660 kcal 600 kcal 93 kcal/g 52/48 37% 1680 kcal 880 kcal 800 kcal c 93 kcal/g 52/48 37% Elettroliti: Fosfato (b) acetato 3,0 mmol 40 mmol 4,5 mmol 60 mmol a m 6,0 mmol 80 mmol pH appross. 6,4 6,4 6,4 Osmolarità. 1170 mosm/L 1170 mosm/L r 1170 mosm/L Per OLIMEL N9 la velocità d'infusione massima è 1,8 mL/kg/ora, corrispondenti a 0,10 g/kg/ora amminoacidi; 0,19 g/kg/ora glucosio e 0,07 g/kg/ora lipidi. Nei bambini di età superiore a due anni Non esistono studi eseguiti sulla popolazione pediatrica. Il dosaggio dipende dal dispendio di energie, dallo stato clinico, dal peso corporeo e dalla capacità di metabolizzare i costituenti di OLIMEL N9 del paziente, oltre che da energia o proteine ulteriori fornite oralmente/enteralmente, pertanto, i formati della sacca devono essere scelti di conseguenza. Inoltre, le esigenze quotidiane di liquidi, azoto ed energia si riducono continuamente con l'età. Sono stati presi in considerazione 2 gruppi, età tra 2 e 11 anni, ed età tra 12 e 18 anni. Per Olimel N9 nel gruppo da 2 a 11 anni di età, i fattori limitanti sono la concentrazione di amminoacidi per la dose giornaliera e la concentrazione dei lipidi per la velocità oraria Nel gruppo da 12 a 18 anni di età, i fattori limitanti sono la concentrazione di amminoacidi sia per la dose giornaliera che per la velocità oraria. Gli apporti risultanti sono mostrati di seguito: Costituenti Da 2 a 11 anni l Da 12 a 18 anni Raccomandatoa e OLIMEL N9 Vol Massimo Raccomandatoa OLIMEL N9 Vol Massimo d Dose massima giornaliera Liquidi (mL/kg/d) 60 – 120 53 50 – 80 45 Amminoacidi (g/kg/d) 1 – 2 (fino a 3) 3 1 – 2 2 Glucosio (g/kg/d) 12 – 14 (fino a 18) a 5,8 3 – 10 (fino a 14) 3,9 Lipidi (g/kg/d) 0,5 - 3 n 2,1 0,5 - 2 (fino a 3) 1,4 Energia totale (kcal/kg/d) 60 – 90 a 56 30 – 75 37 Massima velocità all’ora OLIMEL N9 (mL/kg/h) i 3,3 2,1 Amino acidi(g/kg/h) l 0,20 0,19 0,12 0,12 Glucosio (g/kg/h) a 1,2 0,36 1,2 0,23 Lipidi (g/kg/h) 0,13 0,13 0,13 0,08 a: Valori raccomandati dalla Linee Guida 2005 ESPGHAN/ ESPEN Normalmente, la velocità del flusso si deve aumentare gradualmente durante la prima ora e poi deve essere regolata prendendo in considerazione la dose da somministrare, l’apporto di volume giornaliero e la durata dell’infusione. In generale, nei bambini piccoli si raccomanda di iniziare l'infusione con una dose giornaliera bassa, e di aumentarla gradualmente fino al dosaggio massimo (vedere sopra). Modo e durata di somministrazione Solo per uso singolo. Si raccomanda di usare il contenuto immediatamente dopo l’apertura della sacca e di non conservarlo per un’infusione successiva. Dopo la ricostituzione, la miscela è omogenea e ha un aspetto lattiginoso. Per istruzioni sulla preparazione e la manipolazione dell'emulsione per infusione, vedere il paragrafo 6.6. Per la sua alta osmolarità, OLIMEL N9 può essere somministrato solo attraverso una vena centrale. La durata d'infusione raccomandata per una sacca per nutrizione parenterale è compresa tra 12 e 24 ore. Il trattamento con nutrizione parenterale può proseguire per tutto il tempo richiesto dalle condizioni cliniche del paziente. C.INCOMPATIBILITÀNon aggiungere altro medicinale o altre sostanze a uno qualsiasi dei costituenti della sacca o all'emulsione ricostituita senza averne prima verificato la compatibilità e la stabilità della preparazione risultante (in particolare la stabilità dell'emulsione lipidica). Le incompatibilità possono derivare, ad esempio, da eccessiva acidità (pH basso) o da contenuto non idoneo di cationi bivalenti (Ca e Mg ) che possono destabilizzare l'emulsione di lipidi. Come con qualsiasi altra miscela per la nutrizione parenterale, è necessario prendere in considerazione il rapporto calcio/fosfato. Un’eccessiva aggiunta di calcio e fosfato, in particolar modo sotto forma di sali minerali, può causare la formazione di precipitati di fosfato di calcio. A causa del rischio di precipitazione, OLIMEL N9 non deve essere somministrato attraverso la stessa linea di infusione o mescolato con l’antibiotico ampicillina o l’antiepilettico fosfenitoina. Verificare la compatibilità con le soluzioni somministrate contemporaneamente attraverso lo stesso set di somministrazione, catetere o cannula. Non somministrare prima, contemporaneamente o dopo una emotrasfusione tramite la stessa linea, a causa del rischio di pseudoagglutinazione. D.PRECAUZIONI PARTICOLARI PER LO SMALTIMENTO E LA MANIPOLAZIONEUna visione di insieme degli vari stadi di preparazione per la somministrazione di OLIMEL N9 viene illustrata nella Figura 1 . Apertura Rimuovere l'involucro esterno di protezione. Gettare il sacchetto dell'assorbitore di ossigeno. Verificare l'integrità della sacca e delle membrane di separazione non permanenti. Usare solo se la sacca non è danneggiata, se le membrane di separazione non permanenti sono intatte (cioè non è presente miscelazione del contenuto dei 3 compartimenti), se la soluzione di amminoacidi e la soluzione di glucosio sono limpide, incolori o lievemente gialle, ed in pratica prive di particelle visibili, e se l'emulsione di lipidi è un liquido omogeneo con aspetto lattiginoso. Miscelazione delle soluzioni e dell'emulsione Accertarsi che il prodotto sia a temperatura ambiente quando si rompono le membrane di separazione non permanenti. Arrotolare manualmente la sacca su se stessa, partendo dalla parte alta (estremità con cappio). Le membrane di separazione non permanenti scompariranno dal lato accanto alle aperture. Continuare ad arrotolare la sacca finché le membrane di separazione non siano aperte per circa metà della loro lunghezza. Mescolare la sacca capovolgendola almeno 3 volte. Dopo la ricostituzione la miscela è una emulsione omogenea di aspetto lattiginoso. Aggiunte: La sacca è dotata di una capacità sufficiente a consentire aggiunte, quali vitamine, elettroliti ed elementi in tracce. Un'eventuale aggiunta (incluse le vitamine) va fatta nella miscela ricostituita (dopo l'apertura delle membrane di separazione non permanenti e dopo la miscelazione del contenuto dei tre compartimenti). È possibile aggiungere vitamine anche nel compartimento del glucosio prima che la miscela sia ricostituita (prima dell'apertura delle membrane di separazione non permanenti e prima della miscelazione dei tre compartimenti). Quando si eseguono le aggiunte alle formulazioni contenenti elettroliti, si deve considerare la quantità di elettroliti già presente nella sacca Le aggiunte devono essere effettuate da personale qualificato in condizioni asettiche. OLIMEL N9 si può integrare con elettroliti, sulla base della tabella seguente: e Per 1.000 mL Livello incluso d Aggiunta ulteriore massima Livello totale massimo sodio 0 mmol 150 mmol 150 mmol potassio 0 mmol 150 mmol 150 mmol magnesio 0 mmol a 5,6 mmol 5,6 mmol calcio 0 mmol 5,0 (3,5(a)) mmol 5,0 (3,5a)) mmol Fosfato inorganico 0 mmol n 8,0 mmol 8,0 mmol Fosfato organico 3 mmol (b) a 22 mmol 25 mmol (b) Valore corrispondente all'aggiunta del fosfato inorganico Incluso il fosfato fornito dall'emulsione di lipidi Elementi in tracce e vitamine: La stabilità è stata dimostrata con preparazioni di vitamine e oligoelementi in commercio (contenenti al massimo 1 mg di ferro). La compatibilità di altri additivi è disponibile su richiesta. Nell'effettuare aggiunte, prima della somministrazione in vena periferica, misurare l'osmolarità finale della miscela. Per eseguire un'aggiunta: L'operazione deve avvenire in condizione asettica. Preparare il punto d'iniezione della sacca. Forare il punto di iniezione e iniettare gli additivi mediante un ago per iniezione o un dispositivo di ricostituzione. Miscelare il contenuto della sacca e le aggiunte. Preparazione dell'infusione L'operazione deve avvenire in condizione asettica. Sospendere la sacca. Rimuovere la protezione in plastica dal punto di somministrazione. Inserire saldamente lo spike del set di infusione nel punto di somministrazione. Somministrazione Solo per uso singolo. Somministrare il prodotto solo dopo la rottura delle membrane di separazione non permanenti tra i3 compartments and mixing of the contents of the 3 compartments. Ensure that the final emulsion for infusion does not show evidence of phase separation. After opening the bag, the contents must be used immediately. Never store the bag open for a subsequent infusion. Do not reconnect any partially used bags. Do not connect the bags in series to avoid the possibility of gas embolism due to gas contained in the main bag. Dispose of any unused product, any derived waste, and all necessary devices. Extravasation The catheter site must be checked regularly for possible signs of extravasation. In case of extravasation, administration must be stopped immediately while maintaining the catheter or cannula inserted for immediate patient treatment. If possible, perform an aspiration through the inserted catheter or cannula to reduce the amount of fluid present in the tissues before removing the catheter or cannula. Depending on the extravasated product (including one or more products mixed with OLIMEL N9, if applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken. Treatment options may include non- pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult a plastic surgeon within the first 72 hours. The extravasation site should be monitored at least every 4 hours during the first 24 hours, then once a day. The infusion should not be restarted in the same central vein. OLIMEL N9E emulsion for infusion Read this leaflet carefully before you are given this medicine as it contains important information for you. Keep this leaflet. You may need to read it again. If you have any questions, ask your doctor or nurse. If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4. Contents of this leaflet: 31. What OLIMEL N9E emulsion for infusion is and what it is used for 32. What you need to know before you are given OLIMEL N9E emulsion for infusion 33. How to use OLIMEL N9E, emulsion for infusion 34. Possible side effects 35. How to store OLIMEL N9E emulsion for infusion 36. Contents of the pack and other information 1. What is OLIMEL N9E emulsion for infusion and what is it used for OLIMEL N9E is an emulsion for infusion. It is presented in the form of a 3-compartment bag. One compartment contains a glucose solution with calcium, the second a lipid emulsion and the third a solution of amino acids with other electrolytes. OLIMEL N9E is used to provide nutrition to adults and children over two years of age through a tube into a vein, when normal oral feeding is not suitable. OLIMEL N9E must be used exclusively under medical supervision. 2. What you need to know before you are given OLIMEL N9E emulsion for infusion OLIMEL N9E emulsion for infusion must not be used in the following cases In premature newborns, infants and children under 2 years of age If you are hypersensitive (allergic) to egg proteins, soybean seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the excipients. If the use of certain amino acids creates problems for your body. If you have particularly high levels of fats in your blood. If you suffer from hyperglycemia (too much sugar in the blood). If you have an abnormally high concentration of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood. In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, along with the results of tests performed. Warnings and precautions Consult your doctor or nurse before you are given OLIMEL N9E. If solutions for total parenteral nutrition are administered to you too quickly, this may cause injury or death. The infusion must be stopped immediately if you develop signs or symptoms of an abnormal allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybean seeds and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soy and peanut proteins have been observed. Olimel N9E contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N9E, emulsion for infusion must not be used” above) Difficulty breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, report it to your doctor or nurse, who will decide what actions to take. The antibiotic called ceftriaxone must not be mixed or administered simultaneously with any solution containing calcium (including OLIMEL N9E) that is administered to you via an intravenous drip. These medicines must not be administered together even through different infusion lines or different infusion sites. However, you may take OLIMEL N9E and ceftriaxone in sequence, one after the other, if infusion lines in different locations are used or if the infusion lines are replaced or have been thoroughly washed with saline solution between infusions to avoid the formation of precipitates (calcium-ceftriaxone salt particles). Some drugs and diseases can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. Your doctor will carefully monitor you for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may be at increased risk of developing infections from their medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance, and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk. If you are severely malnourished, to the point of receiving nutrition intravenously, your doctor must start treatment slowly. In addition, the doctor must carefully monitor you to prevent sudden changes in your fluid levels, vitamins, electrolytes and minerals. The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary. The doctor must be informed if: you have a severe kidney problem. You must inform the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment; you have a severe liver problem; you have a blood clotting problem; you have inadequate functioning of the adrenal glands (adrenal insufficiency), which are triangular glands located above the kidneys; you have heart failure; you have lung disease; you have fluid accumulation in the body (hyperhydration); you have insufficient fluid in the body (dehydration); you have high levels of sugar in the blood (diabetes mellitus) that are not being treated; you have a heart attack or stroke secondary to sudden heart failure; you have severe metabolic acidosis (when the blood is too acidic); you have a generalized infection (septicemia); you are in a coma. To verify the effectiveness and overall safety of administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is administered to you for several weeks, your blood will be monitored regularly. The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects). If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, inform your doctor or nurse. The administration will be stopped immediately and restarted in another vein. If your blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N9E or give you a medicine to control your blood sugar level (insulin). OLIMEL N9E can be administered to you through a tube (catheter) into a large vein in the chest (central vein). Children and adolescents If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used. Other medicines andOLIMEL N9E Tell your doctor if you are taking or using, have recently taken or used, or might take or use any other medicine. The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility. OLIMEL N9E must not be administered simultaneously with blood through the same infusion set. OLIMEL N9E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tube, because particles can form. If the same device is used to administer these medicines in succession, the device must be thoroughly washed. Due to the risk of precipitation, OLIMEL N9E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin. The olive and soybean oils in OLIMEL N9E contain vitamin K. This vitamin generally does not affect blood-thinning drugs (anticoagulants), such as coumarin. However, inform your doctor if you are taking anticoagulant drugs. The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them). OLIMEL N9E contains potassium. Take particular care with patients who are taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (drugs for the treatment of hypertension) or immunosuppressants. These types of drugs can increase potassium levels in the blood. Pregnancy, breastfeeding and fertility If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding with breast milk, ask your doctor for advice before taking this medicine. OLIMEL N9E can be considered during pregnancy and breastfeeding if necessary. Driving and operating machinery Not relevant 3. How to use OLIMEL N9E emulsion for infusion Dosage OLIMEL N9E must be administered only to adults and children over two years of age. This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your chest. OLIMEL N9E must be at room temperature before use. OLIMEL N9E is for single use only. The infusion of a bag usually lasts between 12 and 24 hours. Dosage - adults The doctor will specify a flow rate corresponding to your needs and clinical condition. The prescription may continue for as long as required, according to your clinical condition. Dosage - children over two years of age and adolescents The doctor will decide the dose and for how long the medicine will be administered. This will depend on age, weight, height, medical conditions and the body's ability to break down and use the components of OLIMEL N9E. If you have been given more OLIMEL N9E emulsion for infusion than you should If the dose given is too high or the infusion is too fast, the amino acid content may make your blood too acidic and symptoms of hypervolemia (increased blood volume) may occur. Blood and urine glucose levels may increase and a hyperosmolar syndrome (excessive blood viscosity) may develop and the lipid content may increase the level of triglycerides in your blood. Receiving an infusion too quickly or too large a volume of OLIMEL N9E can cause nausea, vomiting, chills, headache, hot flashes, excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be stopped immediately. In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys eliminate the excess product. To prevent such events from happening, the doctor will regularly monitor your condition and test your blood parameters. If you have any doubts about the use of OLIMEL N9E, consult your doctor. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everyone gets them. If you notice any changes in the way you feel, during or after treatment, tell your doctor or nurse promptly. The tests your doctor will perform while you are taking the medicine reduce the risk of side effects. The infusion will be stopped immediately if signs or symptoms of an allergic reaction develop, such as sweating, fever, chills, headache, skin rash or difficulty in breathing. With OLIMEL N9E the following side effects have been reported: Frequency-Common: may affect up to 1 in 10 people Fast heart rate (tachycardia). Decreased appetite. Increased level of fats in the blood (hypertriglyceridemia). Abdominal pain. Diarrhea. Nausea. Increased blood pressure (hypertension). Frequency - Not known: frequency cannot be estimated based on the available data Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site The following side effects have been reported with similar parenteral nutrition products: Frequency- Very rare: may affect up to 1 in 10,000 people Reduced ability to remove fats (fat overload syndrome) associated with a sudden and rapid deterioration of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the lipid emulsion infusion: Fever Reduced red blood cells which can make the skin pale and cause weakness or shortness of breath (anemia). Low white blood cell count, which can increase the risk of infection (leukopenia) Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia) Blood clotting disorders that impair the blood's ability to clot High levels of fats in the blood (hyperlipidemia) Fatty infiltration of the liver (hepatomegaly) Deterioration of liver function Manifestations affecting the central nervous system (e.g., coma). Frequencynot known: frequency cannot be estimated based on the available data Allergic reactions. Abnormal blood test results for liver function. Problems in the elimination of bile (cholestasis) Increased liver size (hepatomegaly). Jaundice (icterus). Reduced number of platelets (thrombocytopenia). Increased levels of nitrogen in the blood (azotemia) Elevated liver enzymes Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress). Reporting of side effects If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system at: http://www.agenziafarmaco.gov.it/content/come- segnalare-una-sospetta-reazione-avversa . By reporting side effects you can help provide more information on the safety of this medicine. 5. How to store OLIMEL N9E emulsion for infusion Keep this medicine out of sight and reach of children. Do not use this medicine after the expiry date that is stated on the container and on the outer packaging (MM/YYYY). The expiry date refers to the last day of the month. Do not freeze. Store in the outer packaging. Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment. 6. Contents of the pack and other information What OLIMEL N9E, emulsion for infusion contains The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at 14.2%(corresponding to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine (as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate, chloride), an emulsion of lipids at20%(corresponding to 20 g/100 mL) (purified olive oil and purified soybean oil) and a solution of glucose at 27.5%(corresponding to 27.5 g/100 mL) (as glucose monohydrate) with calcium. The excipients are: Compartment Lipid emulsion Compartment Amino acid solution Compartment Glucose solution Hydrochloric acid (for pH adjustment), water for injections Appearance of OLIMEL N9E, emulsion for infusion and contents of the packs OLIMEL N9E is an emulsion for infusion packaged in a three-compartment bag. One compartment contains a lipid emulsion, another compartment a solution of Purified egg phospholipid, glycerol, sodium oleate, sodium hydroxide (for pH adjustment), water for injections Glacial acetic acid (for pH adjustment), water for injections amino acids with electrolytes and the third compartment a glucose solution with calcium. These compartments are separated by non-permanent membranes. Before administration, the contents of the compartments must be mixed by rolling the bag on itself starting from the top until the membranes open. Appearance before reconstitution: The amino acid and glucose solutions are clear, clear colorless or slightly yellow. The lipid emulsion is homogeneous with a milky appearance. Appearance after reconstitution: homogeneous emulsion with a milky appearance The 3-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorized additives. To prevent contact with atmospheric oxygen, the bag is packaged in an outer shell with an oxygen barrier, which contains an oxygen absorber sachet. Pack sizes: 1,000 mL bag: 1 box with 6 bags 1,500 mL bag: 1 box with 4 bags 2,000 mL bag: 1 box with 4 bags 1 bag of 1,000 mL, 1,500 mL and 2,000 mL Not all pack sizes may be marketed. Marketing Authorisation Holder Baxter S.p.A. Piazzale dell’Industria 20 00144 Rome Italy Manufacturer: Baxter S.A., Boulevard René Branquart, 80 7860 Lessines Belgium This medicinal product is authorised in the member states of the European Economic Community with the following names: France, Portugal, Estonia, Poland, Lithuania, Bulgaria, Romania, Latvia, Czech Republic, Belgium, Spain, Slovak Republic, Netherlands, Luxembourg, Slovenia, Italy, Denmark, Iceland, Sweden, Norway, Finland, Greece, Cyprus: OLIMEL N9E Austria: ZentroOLIMEL 5,7 % mit Elektrolyten Germany: Olimel 5,7% E United Kingdom, Ireland, Malta: Triomel 9g/L nitrogen 1070 kcal/L with electrolytes Hungary: Olimel 9 g/L nitrogén elektrolitokkal emulziós infúzió  -------------------------------------------------------------------------------------------------------------- The following information is intended exclusively for physicians or healthcare professionals: Pharmacotherapeutic category: Solutions for parenteral nutrition/combinations ATC code: B05 BA10 I.QUALITATIVE AND QUANTITATIVE COMPOSITIONOLIMEL N9E is presented as a 3-compartment bag. Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with other electrolytes: Content per bag 1,000 mL 1,500 mL 2,000 mL Glucose 27.5% solution (corresponding to 27.5 g/100 mL) 400 mL 600 mL 800 mL Amino acid 14.2% solution (corresponding to 14.2 g/100 mL) 400 mL 600 mL 800 mL 20% Lipid emulsion (corresponding to 20 g/100 mL) 200 mL 300 mL 400 mL Composition of the reconstituted emulsion after mixing the contents of the three compartments: Active ingredients1,000 mL1,500 mL2,000 mL Purified olive oil + purified soybean oil 40.00 g 60.00 g 80.00 g Alanine 8.24 g 12.36 g 16.48 g Arginine 5.58 g 8.37 g 11.16 g Aspartic acid 1.65 g 2.47 g 3.30 g Glutamic acid 2.84 g 4.27 g 5.69 g Glycine 3.95 g 5.92 g 7.90 g Histidine 3.40 g 5.09 g 6.79 g Isoleucine 2.84 g 4.27 g 5.69 g Leucine 3.95 g 5.92 g 7.90 g Lysine (as lysine acetate) 8.96 g (12.64 g) Methionine 2.84 g 4.27 g 5.69 g Phenylalanine 3.95 g 5.92 g 7.90 g Proline 3.40 g 5.09 g 6.79 g Serine 2.25 g 3.37 g 4.50 g Threonine 2.84 g 4.27 g 5.69 g Tryptophan 0.95 g 1.42 g 1.90 g Tyrosine 0.15 g 0.22 g 0.30 g Valine 3.64 g 5.47 g 7.29 g Sodium acetate, trihydrate 1.50 g 2.24 g 2.99 g Sodium glycerophosphate hydrate 3.67 g 5.51 g 7.34 g Potassium chloride 2.24 g 3.35 g 4.47 g Magnesium chloride, hexahydrate 0.81 g 1.22 g 1.62 g Calcium chloride, dihydrate 0.52 g 0.77 g 1.03 g Anhydrous glucose (as glucose monohydrate) 4.48 g (6.32 g) 6.72 g (9.48 g) 110.00 g (121.00 g) 165.00 g (181.50 g) 220.00 g (242.00 g) A mixture of purified olive oil (approximately 80%) and purified soybean oil (approximately 20%) corresponding to an essential fatty acids / total fatty acids ratio of 20%. Gli eccipienti sono: Compartimento Emulsione di lipidi Compartimento Soluzione di amminoacidi Compartimento Soluzione di glucosio Acido cloridrico(per l’aggiustamento del pH), acqua per preparazioni iniettabili, Apporto nutritivo della emulsione ricostituita per ciascun formato della sacca: Include calorie da fosfatidi purificati di uovo Include fosfato fornito dall'emulsione di lipidi Fosfatide purificato di uovo, glicerolo, sodio oleato, sodio idrossido (per l’aggiustamento del pH), acqua per preparazioni iniettabili Acido acetico glaciale (per l’aggiustamento del pH), acqua per preparazioni iniettabili 1.000 mL 1.500 mL 2.000 mL Lipidi 40 g a 60 g 80 g Amminoacidi 56,9 g 85,4 g 113,9 g Azoto 9,0 g F 13,5 g 18,0 g Glucosio 110,0 g 165,0 g 220,0 g Energia: Calorie totali appross. Calorie non proteiche. Calorie glucosio Calorie lipidiche..(a) Rapporto calorie non proteiche/azoto Rapporto calorie glucosio/lipidi Calorie lipidiche/totali 1.070 kcal 840 kcal d 440 kcal 400 kcal a 93 kcal/g n 52/48 37% l e 1.600 kcal 1.260 kcal 660 kcal 600 kcal 93 kcal/g 52/48 37% 2.140 kcal 1.680 kcal 880 kcal 800 kcal 93 kcal/g 52/48 37% Elettroliti: sodio potassio l magnesio a calcio Fosfato (b) t acetato cloruro a 35,0 mmol i 30,0 mmol 4,0 mmol 3,5 mmol 15,0 mmol 54 mmol 45 mmol 52,5 mmol 45,0 mmol 6,0 mmol 5,3 mmol 22,5 mmol 80 mmol 68 mmol 70,0 mmol 60,0 mmol 8,0 mmol 7,0 mmol 30,0 mmol 107 mmol 90 mmol I pH. 6,4 6,4 6,4 Osmolarità. 1310 mosm/L 1310 mosm/L 1310 mosm/L J.POSOLOGY AND MODE OF ADMINISTRATION Posology The use of OLIMEL N9E is not recommended in children under 2 years of age due to the inappropriate composition and volume (see paragraphs 4.4, 5.1 and 5.2 of the SmPC). Do not exceed the maximum daily dose reported below. Due to the static composition of the multi-compartment bag, it may not be possible to successfully meet all of the patient's nutritional needs simultaneously. Clinical situations may occur in which patients require varying amounts of nutrients compared to the composition of the static bag. In such a situation, any adjustment of the volume (dose) must take into account the resulting effect that this will have on the dosage of all other nutrients in OLIMEL N9E. For example, pediatric patients may have a requirement greater than 0.2 mmol/kg/day of phosphate. In these circumstances, healthcare professionals may consider adjusting the volume (dose) of OLIMEL N9E in order to meet this increased need. In adults: The dosage depends on energy expenditure, clinical condition, body weight and the patient's ability to metabolize the constituents of OLIMEL N9E, as well as the additional energy or protein provided orally/enterally, therefore the bag sizes must be chosen accordingly. Average daily requirements are: 0.16-0.35 g nitrogen/kg body weight (1-2 g amino acids/kg), depending on the patient's nutritional status and degree of catabolic stress, 20-40 kcal/kg, 20-40 mL fluids /kg or 1-1.5 mL per kcal spent. For OLIMEL N9E the maximum daily dose is defined by the amino acid intake, 35 mL/kg, corresponding to 2.0 g/kg amino acids, 3.9 g/kg glucose, 1.4 g/kg lipids, 1.2 mmol/kg sodium and 1.1 mmol/kg potassium. For a 70 kg patient this would be equivalent to 2,450 mL of OLIMEL N9E per day, which translates to an intake of 140 g amino acids, 270 g glucose and 98 g lipids, (i.e. 2,058 non-protein kcal and 2,622 total kcal). Normally, the flow rate must be increased gradually during the first hour then must be adjusted to account for the dose to be administered, the volumes to be taken daily and the duration of the infusion. For OLIMEL N9E the maximum infusion rate is 1.8 mL/kg/hour, corresponding to 0.10 g/kg/hour amino acids; 0.19 g/kg/hour glucose and 0.07 g/kg/hour lipids. In children over 2 years of age No studies have been conducted in the pediatric population. The dosage depends on energy expenditure, clinical condition, body weight and the patient's ability to metabolize the constituents of OLIMEL N9E, as well as additional energy or protein provided orally/enterally, therefore, the bag sizes must be chosen accordingly. Furthermore, daily requirements for fluids, nitrogen and energy continuously decrease with age. Two groups were considered, age between 2 and 11 years, and age between 12 and 18 years. For Olimel N9E in the 2 to 11 year age group, the limiting factors are the phosphate concentration for the daily dose (0.2 mmol/kg/day) and the lipid concentration for the hourly rate. In the 12 to 18 year age group the limiting factors are the phosphate concentration for the daily dose (0.2 mmol/kg/day) and the amino acid concentration for the hourly rate. The resulting intakes are shown below: e Constituents From 2 to 11 years From 12 to 18 years Recommendeda OLIMEL N9E Vol Maximum Recommendeda OLIMEL N9E Vol Maximum g Maximum daily dose Liquids (mL/kg/d) 60 – 120 13 50 – 80 13 A Amino acids (g/kg/d) 1 – 2 (up to 3) 0,8 1 – 2 0,8 Glucose (g/kg/d) 12 – 14 (up to 18) 1,5 3 – 10 (up to 14) 1,5 Lipids (g/kg/d) 0,5 - 3 0,5 0.5 - 2 (up to 3) 0,5 a: Values recommended by the 2005 ESPGHAN/ ESPEN Guidelines Normally, the flow rate should be increased gradually during the first hour and then must be adjusted taking into account the dose to be administered, the daily volume intake and the duration of the infusion. In general, in young children it is recommended to start the infusion with a low daily dose, and to increase it gradually up to the maximum dosage (see above). Mode and duration of administration For single use only. It is recommended to use the contents immediately after opening the bag and not to store it for a subsequent infusion. After reconstitution, the mixture is homogeneous and has a milky appearance. For instructions on preparation and handling of the infusion emulsion, see paragraph 6.6. Due to its high osmolarity, OLIMEL N9E can only be administered through a central vein. The recommended infusion duration for a parenteral nutrition bag is between 12 and 24 hours. Treatment with parenteral nutrition can continue for as long as required by the patient's clinical condition. F.INCOMPATIBILITIESDo not add any other medicinal product or other substances to any of the bag constituents or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular the stability of the lipid emulsion). Incompatibilities can arise, for example, from excessive acidity (low pH) or from an inappropriate content of divalent cations (Ca and Mg) which can destabilize the lipid emulsion. As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered. Excessive addition of calcium and phosphate, especially in the form of mineral salts, can cause the formation of calcium phosphate precipitates. OLIMEL N9E contains calcium ions which represent a further risk of coagulation in blood or in anticoagulated or citrated blood components. Ceftriaxone must not be mixed or administered concurrently with intravenous solutions containing calcium, including OLIMEL N9E, through the same infusion line (e.g. via a Y-connector) due to the risk of ceftriaxone-calcium salt precipitation (see paragraphs 4.4 and 4.5 of the SmPC). Ceftriaxone and solutions containing calcium can be administered sequentially if different infusion lines are used or if the infusion lines are thoroughly flushed with physiological saline between infusions to avoid the formation of precipitates. Total energy (kcal/kg/d) 60 – 90 14 30 – 75 14 Maximum hourly rate OLIMEL N9E (mL/kg/h) 3,3 o 2,1 Amino acids(g/kg/h) 0,20 0,19 0,12 0,12 Glucose (g/kg/h) 1,2 0,36 1,2 c 0,23 Lipids (g/kg/h) 0,13 0,13 0,13 0,08 Due to the risk of precipitation, OLIMEL N9E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin. Verify compatibility with solutions administered simultaneously through the same infusion set, catheter or cannula. Do not administer before, concurrently with or after a blood transfusion through the same line, due to the risk of pseudoagglutination. G.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING An overview of the various stages of preparation for the administration of OLIMEL N9E is illustrated in Figure 1. Opening Remove the external protective wrapper. Discard the oxygen absorber bag. Check the integrity of the bag and the non-permanent separation membranes. Use only if the bag is undamaged, the non-permanent separation membranes are intact (i.e. no mixing of the contents of the 3 compartments), the amino acid solution and the glucose solution are clear, colorless or slightly yellow, and practically free of visible particles, and the lipid emulsion is a homogeneous liquid with a milky appearance. Mixing of the solutions and the emulsion Ensure that the product is at room temperature when breaking the non-permanent separation membranes. Roll the bag manually from top to bottom (end with loop). The non-permanent separation membranes will disappear on the side next to the openings. Continue rolling the bag until the separation membranes are open for about half their length. Mix the bag by inverting it at least 3 times. After reconstitution the mixture is a homogeneous emulsion with a milky appearance. Additives: The bag is equipped with sufficient capacity to allow additives, such as vitamins, electrolytes and trace elements. Any addition (including vitamins) should be made to the reconstituted mixture (after opening the non-permanent separation membranes and after mixing the contents of the three compartments). Vitamins can also be added to the glucose compartment before the mixture is reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments). When making additions to formulations containing electrolytes, the amount of electrolytes already present in the bag must be considered. Additives must be made by qualified personnel under aseptic conditions. OLIMEL N9E can be supplemented with electrolytes, based on the following table: Corresponding value for the addition of inorganic phosphate Including phosphate provided by the lipid emulsion Trace elements and vitamins: Stability has been demonstrated with commercially available vitamin and trace element preparations (containing a maximum of 1 mg of iron). Compatibility of other additives is available on request. When making additions, measure the final osmolarity of the mixture before administration into a peripheral vein. To make an addition: Work under aseptic conditions. Prepare the injection site on the bag. Puncture the injection site and inject the additives using a syringe needle or a reconstitution device. Mix the contents of the bag and the additives. Preparation of the infusion The operation must be carried out under aseptic conditions. Suspend the bag. Remove the plastic protector from the administration port. Insert the spike of the infusion set firmly into the administration port. d>o Total level maximum
sodium	35 mmol	115 mmol	c 150 mmol
potassium	30 mmol	120 mmol	150 mmol
magnesium	4.0 mmol	1.6 mmol	a 5.6 mmol
calcium	3.5 mmol	1.5 (0.0(a)) mmol	5.0 (3.5(a)) mmol
Inorganic phosphate	0 mmol	3.0 mmol	m 3.0 mmol
Organic phosphate	15 mmol ( b)	10 mmol	25 mmol ( b)

Administration
For single use only.
Administer the product only after breaking the non-permanent separation membranes between the 3
compartments and mixing the contents of the 3 compartments.
Ensure that the final emulsion for infusion does not show evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store the bag
open for a subsequent infusion.
Do not reconnect any partially used bags.
Do not connect the bags in series to avoid the possibility of gas embolism due to gas
contained in the main bag.
Dispose of any unused product, any waste derived from it, and all necessary devices.
Extravasation
The catheter site must be checked regularly for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately while maintaining the
catheter or cannula inserted for immediate patient treatment. If possible, perform
an aspiration through the inserted catheter or cannula to reduce the amount of liquid present
in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N9E, if
applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken.
Treatment options may include non-
pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult a
plastic surgeon within the first 72 hours.
The extravasation site should be monitored at least every 4 hours during the first 24 hours, then
once a day.
The infusion should not be restarted in the same central vein.

OLIMEL

N12 emulsion for infusion

Read this leaflet carefully before you are given this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet:

• 37. What OLIMEL N12 is and what it is used for
• 38. What you need to know before you are given OLIMEL N12 emulsion for infusion
• 39. How to use OLIMEL N12, emulsion for infusion
• 40. Possible side effects
• 41. How to store OLIMEL N12 emulsion for infusion
• 42. Contents of the pack and other information

1. What is OLIMEL N12 emulsion for infusion and what it is used for

OLIMEL N12 is an emulsion for infusion. It is presented in the form of a 3-compartment bag.
One compartment contains a glucose solution, the second a lipid emulsion and the third an
amino acid solution.
OLIMEL N12 is used to provide nutrition to adults and children over two years of age through
a tube into a vein, when normal oral feeding is not suitable.
OLIMEL N12 must be used exclusively under medical supervision.

2. What you need to know before you are given OLIMEL N12 emulsion for infusion

OLIMEL N12 emulsion for infusion must not be used

• In premature newborns, infants and children under 2 years of age
• If you are allergic to egg proteins, soybean seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the other ingredients of this medicine (listed in section 6).
• If the use of certain amino acids causes problems for your body.
• If you have particularly high levels of fats in your blood.
• If you suffer from hyperglycemia (too much sugar in the blood).

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, along with the results of tests performed.

Warnings and precautions
Talk to your doctor or nurse before you are given OLIMEL N12.
If you are given total parenteral nutrition solutions too quickly, this can cause injury or death.
The infusion must be stopped immediately if you develop signs or symptoms of an abnormal allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybean and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soy and peanut proteins have been observed.
Olimel N12 contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N12, emulsion for infusion must not be used” above).
Difficulty breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, tell your doctor or nurse, who will decide what action to take.
Some medicines and diseases can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. Your doctor will carefully monitor you for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may be at greater risk of developing infections from their medical conditions. The use of aseptic (germ-free) techniques during catheter placement, and maintenance of the catheter and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk.
If you are severely malnourished, to the point of receiving nutrition intravenously, your doctor must start treatment slowly. In addition, the doctor must carefully monitor you to prevent sudden changes in your fluid levels, vitamins, electrolytes and minerals.
The balance of water and salt in your body and disturbances of metabolism will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary.
Liver disorders including problems with the elimination of bile (cholestasis), fat accumulation (hepatic steatosis), fibrosis, which could lead to liver failure, as well as cholecystitis and cholelithiasis have been reported in patients receiving parenteral nutrition. The cause of these disorders is believed to be due to multiple factors and may differ between patients. If you experience symptoms such as nausea, vomiting, abdominal pain, jaundice of the skin or eyes, consult your doctor to allow identification of possible causative and contributing factors and possible therapeutic and preventive measures.
The doctor must be informed if:

• you have a severe kidney problem. You must tell the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment;
• you have a severe liver problem;
• you have a blood clotting problem;
• your adrenal glands are not functioning properly (adrenal insufficiency), which are triangular glands located above the kidneys;
• you have heart failure;
• you have lung disease;
• you have an accumulation of water in the body (hyperhydration);
• you have insufficient water in the body (dehydration);
• you have high levels of sugar in the blood (diabetes mellitus) that are not being treated;
• you have a heart attack or cardiogenic shock secondary to sudden heart failure;
• you have severe metabolic acidosis (when the blood is too acidic);
• you have a generalized infection (septicemia);
• you are in a coma.

To check the effectiveness and overall safety of the administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is given to you for several weeks, your blood will be monitored regularly.
The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects).
If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, tell your doctor or nurse. The administration will be stopped immediately and restarted in another vein.
If your blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N12 or give you a medicine to control your blood sugar level (insulin).
OLIMEL N12 can be given to you through a tube (catheter) into a large vein in the chest (central vein).

Children and adolescents
If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Supplementation with vitamins and trace elements is always required. Pediatric formulations should be used.

Other medicines and OLIMEL N12
Tell your doctor if you are taking or using, have recently taken or used, or might take or use any other medicines.
The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility.
Tell your doctor if you are taking or receiving any of the following:

• insulin
• heparin

OLIMEL N12 must not be administered simultaneously with blood through the same infusion set.
Due to the risk of precipitation, OLIMEL N12 must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.
The olive and soybean oils in OLIMEL N12 contain vitamin K. This vitamin generally does not affect blood-thinning medications (anticoagulants), such as coumarin. However, tell your doctor if you are taking anticoagulant medications.
The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them).

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning a pregnancy, or if you are breastfeeding, ask your doctor for advice before taking this medicine.
There is no adequate experience with the use of OLIMEL N12 in pregnant or breastfeeding women.
OLIMEL N12 may be considered during pregnancy and breastfeeding, if necessary. OLIMEL N12 should only be given to pregnant or breastfeeding women after careful evaluation.

Fertility
No adequate data are available

Driving and using machines
Not relevant

3. How to use OLIMEL N12 emulsion for infusion

Dosage
OLIMEL N12 must be administered only to adults and children over two years of age.
This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your
chest.
OLIMEL N12 must be at room temperature before use.
OLIMEL N12 is for single use only.
The infusion of a bag usually lasts between 12 and 24 hours.

Dosage - adults
The doctor will specify a flow rate corresponding to your needs and clinical condition.
The prescription may continue for as long as required, according to your clinical condition.

Dosage - children over two years of age and adolescents
The doctor will decide the dose and for how long the medicine will be administered. This will depend
on age, weight, height, medical conditions and the body's ability to break down and use the
components of OLIMEL N12.

If you have been given more OLIMEL N12emulsion for infusion than you should
If the dose given is too high or the infusion is too fast, the amino acid content may make your
blood too acidic and symptoms of hypervolemia (increased blood volume) may occur.
Blood and urine glucose levels may increase and a hyperosmolar syndrome (excessive blood viscosity) may develop and the lipid content may increase the
level of triglycerides in your blood. Receiving an infusion that is too fast or a volume of
OLIMEL N12 that is too large can cause nausea, vomiting, chills, headache, hot flashes,
excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be
stopped immediately.
In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys
eliminate the excess product.
To prevent such events from happening, the doctor will regularly monitor your condition and test
your blood parameters.
If you have any doubts about the use of OLIMEL N12, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you notice any changes in how you feel, during or after treatment, tell your doctor or nurse promptly.
The tests your doctor will perform while you are taking the medicine reduce the risk of side effects.
The infusion must be stopped immediately in case of development of signs or symptoms of an abnormal
allergic reaction, such as sweating, fever, chills, headache, skin rash or difficulty breathing.
With OLIMEL the following side effects have been reported:

Frequency-Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia).
• Decreased appetite.
• Increased levels of fats in the blood (hypertriglyceridemia).
• Abdominal pain.
• Diarrhea.
• Nausea.
• Increased blood pressure (hypertension).

Frequency - Not known: the frequency cannot be defined based on the available data

• Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site

The following side effects have been reported with similar parenteral nutrition products:

Frequency- Very rare: may affect up to 1 in 10,000 people

• Reduced ability to remove lipids (fat overload syndrome) associated with a sudden and sharp deterioration of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after discontinuation of the lipid emulsion infusion:
• Fever
• Reduced red blood cells which can make the skin pale and cause weakness or shortness of breath (anemia).
• Low white blood cell count, which can increase the risk of infection (leukopenia)
• Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia)
• Coagulation disorders that impair the blood's ability to clot
• High levels of fats in the blood (hyperlipidemia)
• Hepatic lipid infiltration (hepatomegaly)
• Deterioration of liver function
• Manifestations involving the central nervous system (e.g., coma).

Frequencynot known: the frequency cannot be established based on the available data

• Allergic reactions.
• Abnormal blood test results for liver function.
• Problems with bile excretion (cholestasis)
• Increased liver size (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus).
• Reduced number of platelets (thrombocytopenia)
• Increased levels of nitrogen in the blood (azotemia)
• Elevated liver enzymes
• Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-
una-sospetta-reazione-avversa . By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store OLIMEL N12 emulsion for infusion

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the container and on the
outer packaging (MM/YYYY). The expiry date refers to the last day of that
month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What OLIMEL N12, emulsion for infusion contains
The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at
14.2%(corresponding to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) (, an emulsion of lipids at17.5%(corresponding to 17.5 g/100
mL) (purified olive oil and purified soybean oil) and a solution of glucose at 27.5%
(corresponding to 27.5 g/100 mL) (as glucose monohydrate).

The otherexcipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution
Compartment
Glucose solution
Hydrochloric acid (for
pH adjustment),
water for injections

Appearance of OLIMEL N12, emulsion for infusion and contents of the pack
OLIMEL N12 is an emulsion for infusion packaged in a three-compartment bag. One
compartment contains a lipid emulsion, another compartment an amino acid solution and the third compartment a glucose solution. These compartments are
separated by non-permanent membranes. Before administration, the contents of the
compartments must be mixed by rolling the bag on itself starting from the top until
the membranes open.
Appearance before reconstitution:
Purified egg phospholipid, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections
The amino acid and glucose solutions are clear, colorless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: homogeneous milky emulsion
The 3-compartment bag is a multi-layer plastic bag. The material of the inner layer (of
contact) of the bag is designed to be compatible with the constituents and authorized additives.

Pack sizes:
650 mL bag: 1 box with 10 bags
1000 mL bag: 1 box with 6 bags
1500 mL bag: 1 box with 4 bags
2000 mL bag: 1 box with 4 bags
1 bag of 650 mL, 1000 mL, 1500 mL and 2000 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Baxter S.p.A.
Piazzale dell’Industria 20
00144 Rome
Italy

Manufacturer:
Baxter S.A.,
Boulevard René Branquart, 80
7860 Lessines
Belgium

This medicinal product is authorised in the member states of the European economic community with the following
names:
Belgium, Czech Republic, France, Greece, Italy, Luxembourg, The Netherlands, Slovenia, Spain:

Austria:

Germany:
>
Denmark, Iceland, Sweden, Norway, Finland, Portugal:

Ireland, Malta, The United Kingdom:
< TRIOMEL 12 g/l nitrogen 950 kcal
 --------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for doctors or healthcare professionals:

• K.QUALITATIVE AND QUANTITATIVE COMPOSITIONOLIMEL N12 is presented as a 3-compartment bag. Each bag contains a glucose solution, a lipid emulsion and an amino acid solution:

Composition of the reconstituted emulsion after mixing the contents of the three compartments:

The excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution
Compartment
Glucose solution
Hydrochloric acid (for
pH adjustment),
water for injections
Nutritional contribution of the reconstituted emulsion for each bag size:
Purified egg phospholipid, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections

DOSAGE AND ADMINISTRATION
Dosage
The use of OLIMEL N12 is not recommended in children under 2 years of age due to the composition
and inadequate volume (see paragraphs 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose reported below. Due to the static composition
of the multi-compartment bag, it may not be possible to simultaneously meet
all of the patient's nutritional needs. Clinical situations may occur in which patients
require varying amounts of nutrients compared to the composition of the static bag. In such
situations, any adjustment of the volume (dose) must take into consideration the effect
resulting from this on the dosage of all other nutrients in OLIMEL N12. In these
circumstances, healthcare professionals may consider adjusting the volume
(dose) of OLIMEL N12 in order to meet this increased need.

In adults:
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N12, as well as additional energy or protein
provided orally/enterally, therefore the bag formats must be chosen accordingly.
Average daily requirements are:

• 0.16-0.35 g nitrogen/kg body weight (1-2 g of amino acids/kg), depending on the patient's nutritional status and the degree of catabolic stress. Special populations may require up to 0.4 g of nitrogen / kg of body weight (2.5 g of amino acids / kg).
• 20-40 kcal/kg,
• 20-40 mL fluids /kg or 1-1.5 mL per kcal spent.

For OLIMEL N12, the maximum daily dose is defined by the amino acid intake, 26 mL/kg,
corresponding to 2.0 g/kg amino acids, 1.9 g/kg glucose, 0.9 g/kg lipids. For a 70 kg patient
this would be equivalent to 1820 mL of OLIMEL N12 per day, which translates to an intake of 138 g
amino acids, 133 g glucose and 64 g lipids (i.e. 1171 non-protein kcal and 1723 total kcal).

In continuous renal replacement therapy (CRRT):For OLIMEL
N12, the maximum daily dose is defined by amino acid intake, 33 ml/ kg corresponding
to 2.5 g / kg of amino acids, 2.4 g/ kg of glucose, 1.2 g/ kg of lipids. For a 70 kg patient, this
would equate to 2310 ml of OLIMEL N12
per day, resulting in an intake of 175 g of amino acids, 169 g of glucose and 81 g of lipids (i.e.
1486 non-protein kcal and 2187 total kcal).

In patients with pathological obesity: the dosage must be calculated based on ideal body weight (IBW). For OLIMEL N12, the maximum daily dose is defined by amino acid intake,
33 ml/kg of IBW corresponding to 2.5 g/kg of amino acids, 2.4 g/kg of glucose, 1.2 g/kg of lipids. For a
70 kg patient, this would equate to 2310 ml of OLIMEL N12 per day, resulting in
an intake of 175 g of amino acids, 169 g of glucose and 81 g of lipids (i.e. 1486 non-protein kcal and
2187 total kcal).
Normally, the flow rate must be gradually increased during the first hour
then must be adjusted to take into account the dose to be administered, the volumes to be taken
daily and the duration of the infusion.
For OLIMEL N12 the maximum infusion rate is 1.3 mL/kg/hour, corresponding to 0.10 g/kg/hour of
amino acids; 0.10 g/kg/hour of glucose and 0.05 g/kg/hour of lipids.

In children over 2 years of age and adolescents
Studies in the pediatric population have not been conducted.
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N12, as well as additional energy or protein
provided orally/enterally, therefore, the bag formats must be chosen accordingly.
In addition, daily fluid, nitrogen and energy requirements continuously decrease with age.
2 groups were considered, between 2 and 11 years of age, and ages between 12 and 18 years of age.
For Olimel N12 in the 2 to 11 year age group, the amino acid concentration is the
limiting factor for the daily dosage and for the hourly rate.
In the 12 to 18 year age group, the amino acid concentration is the limiting factor for
daily dosage and hourly rate.
The resulting intakes are shown below:

Normally, the flow rate must be gradually increased during the first hour and then
must be adjusted taking into consideration the dose to be administered, the volume
daily intake and the duration of the infusion.
In general, in young children it is recommended to start the infusion with a low daily dose, and
to gradually increase it to the maximum dosage (see above).
The maximum infusion rate is 2.6 ml/kg/hour in children between 2 and 11 years of age and 1.6
ml/kg/hour in children between 12 and 18 years of age.
Method and duration of administration
For single use only.
It is recommended to use the contents immediately after opening the bag and not
to store it for a subsequent infusion.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on preparation and handling of the emulsion for infusion, see paragraph

• 6.6 of the Summary of Product Characteristics.

Due to its high osmolarity, OLIMEL N12 must be administered only through a central vein.
The recommended infusion duration for a parenteral nutrition bag is between 12 and 24
hours.
Treatment with parenteral nutrition may continue for as long as required by the patient's clinical conditions.

• G.INCOMPATIBILITIESDo not add any other medicinal product or other substances to any of the bag constituents or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular the stability of the lipid emulsion).

Incompatibilities may arise, for example, from excessive acidity (low pH) or from an inadequate content of divalent cations (Ca and Mg) that can destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be taken into
consideration. Excessive addition of calcium and phosphate, particularly
in the form of mineral salts, can cause the formation of calcium phosphate precipitates.
Due to the risk of precipitation, OLIMEL N12 must not be administered through the same
infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.
Verify compatibility with solutions administered simultaneously through the same
infusion set, catheter or cannula.
Do not administer before, simultaneously with or after a blood transfusion through the same line,
due to the risk of pseudoagglutination.

• H.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING

An overview of the various stages of preparation for the administration of OLIMEL N12 is
illustrated in Figure 1.
Opening
Remove the outer protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the
bag is not damaged, if the non-permanent separation membranes are intact (i.e. no
mixing of the contents of the 3 compartments), if the amino acid solution and the
glucose solution are clear, colorless or slightly yellow, and practically free of visible particles,
and if the lipid emulsion is a homogeneous liquid with a milky appearance.
Mixing of solutions and emulsion
Ensure that the product is at room temperature when breaking the non-permanent separation membranes.
Roll the bag manually on itself, starting from the top (end with loop). The
non-permanent separation membranes will disappear from the side next to the openings. Continue
to roll the bag until the separation membranes are open for about half their
length.
Mix the bag by inverting it at least 3 times.
After reconstitution the mixture is a homogeneous emulsion with a milky appearance.
Additives:
The bag is equipped with sufficient capacity to allow for additives, such as vitamins, electrolytes and
trace elements.
Any addition (including vitamins) must be made to the reconstituted mixture (after opening the
non-permanent separation membranes and after mixing the contents of the three
compartments).
Vitamins can also be added to the glucose compartment before the mixture is
reconstituted (before opening the non-permanent separation membranes and before mixing the three compartments).
Additives must be made by qualified personnel under aseptic conditions.
The OLIMEL N12 formulation can be supplemented with electrolytes, inorganic/organic phosphate and
commercially available multi-vitamin (such as Cernevit) and multi-
trace element preparations (such as Nutryelt). The maximum total levels of additives listed in the following table are
demonstrated by stability data and should not be considered dosage recommendations.
Supplementation should be dictated by the patient's clinical needs and should not exceed
nutritional guidelines. Electrolytes already present in the bag should be taken
into consideration when reaching the maximum total level.
Compatibility may vary between products from different sources and healthcare professionals are
advised to carry out appropriate checks when mixing OLIMEL N12 with other parenteral solutions.

When making additions, measure the final osmolarity of the mixture before administration into a peripheral vein.
To make an addition:

• Operate under aseptic conditions.
• Prepare the injection site of the bag.
• Puncture the injection site and inject the additives using an injection needle or a reconstitution device.
• Mix the contents of the bag and the additives.

Validity After Reconstitution:
Chemical and physical stability during use has been demonstrated for 7 days at 2°C - 8°C, followed by 48 hours
at a temperature not exceeding 30°C.
From a microbiological point of view, the product must be used immediately. If not
used immediately, the storage times and conditions in use before use are
the responsibility of the user and should normally not exceed 24 hours at 2-8 °C, unless
reconstitution has taken place under controlled and validated aseptic conditions.

Validity After Adding Supplements:
For specific mixtures, chemical and physical stability in use has been demonstrated for 7 days at 2°C - 8°C,
followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological point of view, any mixture must be used immediately. Otherwise, the storage times and conditions in use after mixing and before use are
the responsibility of the user and should not normally exceed 24 hours, at 2°C- 8°C, unless
the addition of supplements has taken place under controlled and validated aseptic conditions.
Infusion Preparation
The operation must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic protection from the administration port.
Firmly insert the spike of the infusion set into the administration port.

Figure 1. Procedure for the administration of OLIMEL

Administration
For single use only
Administer the product only after breaking the non-permanent separation membranes between the 3
compartments and mixing the contents of the 3 compartments.
Ensure that the final emulsion for infusion does not show evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store the bag
open for a subsequent infusion.
Do not reconnect any partially used bags.
Do not connect the bags in series to avoid the possibility of gaseous embolism due to the gas contained
in the main bag.
Dispose of any unused product, any waste derived from it, and all necessary devices.
Extravasation
The catheter site must be checked regularly for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately while maintaining the
catheter or cannula inserted for immediate patient treatment. If possible, perform
aspiration through the inserted catheter or cannula to reduce the amount of fluid present
in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N12, if
applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken.
Treatment options may include non-
pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult the
plastic surgeon within the first 72 hours.
The extravasation site should be monitored at least every 4 hours during the first 24 hours, then
once a day.
The infusion should not be restarted in the same central vein.
OLIMEL
N12E emulsion for infusion

Read this leaflet carefully before you are given this medicine as it
contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you get any side effects, see your doctor or nurse. See section 4.

Contents of this leaflet:

• 43. What OLIMEL N12E is and what it is used for
• 44. What you need to know before you are given OLIMEL N12E emulsion for infusion
• 45. How to use OLIMEL N12E, emulsion for infusion
• 46. Possible side effects
• 47. How to store OLIMEL N12E emulsion for infusion
• 48. Contents of the pack and other information

1. What is OLIMEL N12E emulsion for infusion and what is it used for

OLIMEL N12E is an emulsion for infusion. It is presented in the form of a 3-compartment bag.
One compartment contains a glucose solution with calcium, the second a lipid emulsion and the
third a solution of amino acids with other electrolytes.
OLIMEL N12E is used to provide nutrition to adults and children over two years of age through
a tube into a vein, when normal oral feeding is not suitable.
OLIMEL N12E must be used exclusively under medical supervision.

2. What you need to know before you are given OLIMEL N12E emulsion for infusion

OLIMEL N12E emulsion for infusion must not be used

• In premature newborns, infants and children under 2 years of age
• If you are allergic to egg proteins, soybean seeds, peanuts or corn/corn-derived products (see also the “Warnings and precautions” section below), or to any of the other ingredients of this medicine (listed in section 6).
• If the use of certain amino acids causes problems for your body.
• If you have particularly high levels of fats in your blood.
• If you suffer from hyperglycemia (too much sugar in the blood).
• If you have an abnormally high concentration of any of the electrolytes (sodium, potassium, magnesium, calcium and/or phosphorus) in your blood.

In all cases, your doctor will decide whether you should receive this medicine based on factors such as age, weight and medical condition, together with the results of tests performed.

Warnings and precautions
Talk to your doctor or nurse before you are given OLIMEL N12E.
If total parenteral nutrition solutions are given to you too quickly, this can cause injury or death.
The infusion must be stopped immediately if you develop signs or symptoms of an abnormal allergic reaction (such as sweating, fever, chills, headache, skin rash or difficulty breathing). This medicine contains soybean oil and egg phospholipids. Soybean seeds and egg proteins can cause hypersensitivity reactions. Allergic cross-reactions between soybean and peanut proteins have been observed.
Olimel N12E contains glucose derived from corn which may cause hypersensitivity reactions if you are allergic to corn or products derived from corn (see section “OLIMEL N12E, emulsion for infusion must not be used” above).
Difficulty breathing may also be a sign that small particles have formed, blocking blood vessels in the lungs (pulmonary vascular precipitates). If you experience difficulty breathing, tell your doctor or nurse, who will decide what action to take.
The antibiotic called ceftriaxone must not be mixed or given simultaneously with any solution containing calcium (including OLIMEL N12E) that is administered to you via a vein.
These medicines must not be given together even through separate infusion lines or different infusion sites.
However, you may take OLIMEL N12E and ceftriaxone sequentially, one after the other, if different infusion lines are used or if the infusion lines are replaced or thoroughly flushed with saline solution between infusions to avoid the formation of precipitates (calcium-ceftriaxone salt particles).
Some medicines and illnesses can increase the risk of developing infection or sepsis (bacteria in the blood). There is a particular risk of infection or sepsis when a tube (central venous catheter) is inserted into a vein. Your doctor will monitor you closely for any signs of infection. Patients who require parenteral nutrition (nutrition through a tube placed in a vein) may be at increased risk of developing infections from their medical conditions. The use of aseptic techniques (germ-free) during catheter placement and maintenance and during the preparation of the nutritional formula (total parenteral nutrition) can reduce this risk.
If you are severely malnourished, to the point of receiving nutrition intravenously, your doctor must start treatment slowly. In addition, the doctor must monitor you carefully to prevent sudden changes in your fluid levels, vitamins, electrolytes and minerals.
The balance of water and salt in your body and metabolic disorders will be corrected before starting the infusion. The doctor will monitor your condition while you receive this medicine and may adjust the dose or give you additional nutrients, such as vitamins, electrolytes and trace elements, if they deem it necessary.
Liver disorders including problems with the elimination of bile (cholestasis), fat accumulation (hepatic steatosis), fibrosis, which may lead to liver failure, as well as cholecystitis and cholelithiasis have been reported in patients receiving intravenous nutritional therapy. The cause of these disorders is believed to be due to multiple factors and may differ between patients. If you suffer from symptoms such as nausea, vomiting, abdominal pain, jaundice of the skin or eyes, consult your doctor to allow identification of possible causal and contributing factors and possible therapeutic and preventive measures.
The doctor must be informed if:

• you have a severe kidney problem. You must tell the doctor if you are on dialysis (artificial kidney) or if you are undergoing another blood purification treatment;
• you have a severe liver problem;
• you have a blood clotting problem;
• your adrenal glands are not functioning properly (adrenal insufficiency), which are triangular glands located above the kidneys;
• you have heart failure;
• you have a lung disease;
• you have an accumulation of water in the body (hyperhydration);
• you have insufficient water in the body (dehydration);
• you have high levels of sugar in the blood (diabetes mellitus) that are not being treated;
• you have a heart attack or cardiogenic shock secondary to sudden heart failure;
• you have severe metabolic acidosis (when the blood is too acidic);
• you have a generalized infection (septicemia);
• you are in a coma.

To verify the effectiveness and overall safety of administration, the doctor will perform clinical and laboratory tests while you receive this medicine. If this medicine is given to you for several weeks, your blood will be monitored regularly.
The reduced ability of the body to remove the fats contained in this medicine can cause a “fat overload syndrome” (see section 4 - Possible side effects).
If you experience pain, burning or swelling at the infusion site or leakage of the infusion solution during the infusion, tell your doctor or nurse. The administration will be stopped immediately and restarted in another vein.
If your blood sugar level becomes too high, the doctor will adjust the flow rate of OLIMEL N12E or give you a medicine to control your blood sugar level (insulin).
OLIMEL N12E can be given to you through a tube (catheter) into a large vein in the chest (central vein).

Children and adolescents
If the patient is under 18 years of age, particular attention will be paid to providing the correct dosage. Greater precautions will also be taken for the increased sensitivity of children to the risk of infection. Vitamin and trace element supplementation is always required. Pediatric formulations should be used.

Other medicines and OLIMEL N12E
Tell your doctor if you are taking or using, have recently taken or used, or might take or use any other medicine.
The simultaneous assimilation of other medicines is generally not a contraindication. If you are taking other medicines, with or without a prescription, inform your doctor in advance to verify their compatibility.
Tell your doctor if you are taking or receiving any of the following:

• insulin
• heparin

OLIMEL N12E must not be administered simultaneously with blood through the same infusion set.
OLIMEL N12E contains calcium. It must not be administered together with the antibiotic ceftriaxone or through the same tube, because particles can form. If you use the same device to administer these medicines in succession, the device must be thoroughly flushed.
Due to the risk of precipitation, OLIMEL N12E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.
The olive and soybean oils in OLIMEL N12E contain vitamin K. This vitamin generally does not affect blood-thinning medicines (anticoagulants), such as coumarin. However, tell your doctor if you are taking anticoagulant medicines.
The lipids contained in this emulsion can interfere with the results of some laboratory tests if the blood sample is taken before the lipids are eliminated from your blood (which are usually eliminated after a period of 5 or 6 hours without receiving them).
OLIMEL N12E contains potassium. Take particular care with patients who are taking diuretics, ACE inhibitors, angiotensin II receptor antagonists (medicines for the treatment of hypertension) or immunosuppressants. These types of medicines can increase potassium levels in the blood.

Pregnancy, breastfeeding
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor for advice before taking this medicine.
There is no adequate experience with the use of OLIMEL N12E in pregnant or breastfeeding women.
OLIMEL N12E may be considered during pregnancy and breastfeeding if necessary. OLIMEL N12E should only be given to pregnant or breastfeeding women after careful evaluation.

Fertility
No adequate data are available

Driving and operating machinery
Not relevant

3. How to use OLIMEL N12E emulsion for infusion

Dosage
OLIMEL N12E must be administered only to adults and children over two years of age.
This is an emulsion for infusion, to be administered via a tube (catheter) into a vein in your
chest.
OLIMEL N12E must be at room temperature before use.
OLIMEL N12E is for single use only.
The infusion of a bag usually lasts between 12 and 24 hours.

Dosage - adults
The doctor will specify a flow rate corresponding to your needs and clinical condition.
The prescription may continue for as long as required, according to your clinical condition.

Dosage - children over two years of age and adolescents
The doctor will decide the dose and for how long the medicine will be administered. This will depend
on age, weight, height, medical conditions and the body's ability to break down and use the
components of OLIMEL N12E.

If you have been given too much OLIMEL N12Eemulsion for infusion
If the dose given is too high or the infusion is too fast, the amino acid content may make your
blood too acidic and symptoms of hypervolemia (increased circulating blood volume) may occur. Blood and urine glucose levels may increase and a
hyperosmolar syndrome (excessive blood viscosity) may develop, and the lipid content may increase the
level of triglycerides in your blood. Receiving an infusion too quickly or too large a volume of
OLIMEL N12E can cause nausea, vomiting, chills, headache, hot flashes,
excessive sweating (hyperhidrosis) and electrolyte disturbances. In such situations the infusion must be
stopped immediately.
In some severe cases, the doctor may temporarily subject you to renal dialysis to help your kidneys
eliminate the excess product.
To prevent such events from happening, the doctor will regularly monitor your condition and test
your blood parameters.
If you have any doubts about the use of OLIMEL N12E, please consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any changes in the way you feel, during or after treatment, tell your
doctor or nurse promptly.
The tests that your doctor will perform while you are taking the medicine reduce the risk of side
effects.
The infusion must be stopped immediately in case of development of signs or symptoms of
allergic reaction, such as sweating, fever, chills, headache, skin rash or difficulty in
breathing.
With OLIMEL the following side effects have been reported:

Frequency-Common: may affect up to 1 in 10 people

• Fast heart rate (tachycardia).
• Decreased appetite.
• Increased levels of fats in the blood (hypertriglyceridaemia).
• Abdominal pain.
• Diarrhoea.
• Nausea.
• Increased blood pressure (hypertension).

Frequency - Not known: frequency cannot be estimated from the available data

• Leakage of the infusion into the surrounding tissue (extravasation) which can cause pain, irritation, swelling/edema, redness (erythema)/heat, death of tissue cells (skin necrosis) or blisters/vesicles, inflammation, thickening or constriction of the skin at the infusion site

The following side effects have been reported with similar parenteral nutrition products:

Frequency- Very rare: may affect up to 1 in 10,000 people

• Reduced ability to remove lipids (fat overload syndrome) associated with a sudden and rapid deterioration of the patient's medical condition. The following symptoms of fat overload syndrome are usually reversible after stopping the infusion of the lipid emulsion:
• Fever
• Reduced red blood cells which can make the skin pale and cause weakness or shortness of breath (anaemia).
• Low white blood cell count, which can increase the risk of infection (leucopenia)
• Low platelet count, which can increase the risk of bruising and/or bleeding (thrombocytopenia)
• Blood clotting disorders that impair the blood's ability to clot
• High levels of fats in the blood (hyperlipidaemia)
• Fatty infiltration of the liver (hepatomegaly)
• Worsening of liver function
• Manifestations involving the central nervous system (e.g., coma).

Frequencynot known: frequency cannot be estimated from the available data

• Allergic reactions.
• Abnormal blood test results for liver function.
• Problems with the elimination of bile (cholestasis)
• Increased liver size (hepatomegaly)
• Liver disease associated with parenteral nutrition (see "Warnings and precautions" in section 2)
• Jaundice (icterus).
• Reduced number of platelets (thrombocytopenia)
• Increased levels of nitrogen in the blood (azotaemia)
• Elevated liver enzymes
• Formation of small particles that can cause blockage of blood vessels in the lungs (pulmonary vascular precipitates) and cause pulmonary embolism and difficulty breathing (respiratory distress).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. You can also report side effects directly through the
national reporting system at: www.agenziafarmaco.gov.it/content/come-segnalare-
una-sospetta-reazione-avversa . By reporting side effects you can help provide
more information on the safety of this medicine.

5. How to store OLIMEL N12E emulsion for infusion

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date which is stated on the container and on the
outer packaging (MM/YYYY). The expiry date refers to the last day of
that month.
Do not freeze.
Store in the outer packaging.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What OLIMEL N12E, emulsion for infusion contains
The active substancesof each bag of the reconstituted emulsion are a solution of L-amino acids at
14.2%(corresponding to 14.2 g/100 mL) (alanine, arginine, glycine, histidine, isoleucine, leucine, lysine
(as lysine acetate), methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine,
aspartic acid, glutamic acid) with electrolytes (sodium, potassium, magnesium, phosphate, acetate,
chloride), an emulsion of lipids at17.5%(corresponding to 17.5 g/100 mL) (purified olive oil and
purified soybean oil) and a solution of glucose at 27.5%(corresponding to 27.5 g/100 mL) (as
glucose monohydrate) with calcium.

The other excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution and
Compartment
Glucose and
electrolytescalcium
Hydrochloric acid (for
pH adjustment),
water for injections

Appearance of OLIMEL N12E, emulsion for infusion and contents of the pack
OLIMEL N12E is an emulsion for infusion packaged in a three-compartment bag. One
compartment contains a lipid emulsion, another compartment an amino acid solution with electrolytes and the third compartment a glucose solution with calcium. These
Purified egg phosphatide, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections
compartments are separated by non-permanent membranes. Before administration, the
contents of the compartments must be mixed by rolling the bag on itself starting
from the top until the membranes open.
Appearance before reconstitution:
The amino acid and glucose solutions are clear, colorless or slightly yellow.
The lipid emulsion is homogeneous with a milky appearance.
Appearance after reconstitution: homogeneous emulsion with a milky appearance
The 3-compartment bag is a multi-layer plastic bag. The material of the inner (contact) layer of the bag is designed to be compatible with the constituents and authorized additives.

Packs:
650 mL bag: 1 box with 10 bags
1000 mL bag: 1 box with 6 bags
1500 mL bag: 1 box with 4 bags
2000 mL bag: 1 box with 4 bags
1 bag of 650 mL, 1000 mL, 1500 mL and 2000 mL
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Baxter S.p.A.
Piazzale dell’Industria 20
00144 Rome
Italy

Manufacturer:
Baxter S.A.,
Boulevard René Branquart, 80
7860 Lessines
Belgium

This medicinal product is authorised in the member states of the European economic community with the following
names:
Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, France, Greece, Italy, Latvia, Lithuania,
Luxemburg, The Netherlands, Romania, Slovenia, Slovakia, Spain:

Austria:

Germany:
>
Denmark, Iceland, Sweden, Norway, Finland, Poland, Portugal:

Ireland, Malta, The United Kingdom:

Hungary:
< Olimel 12 g/l nitrogén elektrolitokkal emulziós infúzió
 --------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:

• L.QUALITATIVE AND QUANTITATIVE COMPOSITIONOLIMEL N12E is presented as a 3-compartment bag. Each bag contains a glucose solution with calcium, a lipid emulsion and an amino acid solution with other electrolytes:

Composition of the reconstituted emulsion after mixing the contents of the three compartments:

The excipients are:
Compartment
Lipid emulsion
Compartment
Amino acid solution and
Compartment
Glucose and
electrolytescalcium
Hydrochloric acid (for
pH adjustment),
water for injections
Nutritional contribution of the reconstituted emulsion for each bag size:
Purified egg phosphatide, glycerol,
sodium oleate, sodium hydroxide (for
pH adjustment), water for
injections
Glacial acetic acid (for
pH adjustment), water
for injections

DOSAGE AND ADMINISTRATION
Dosage
The use of OLIMEL N12E is not recommended in children under 2 years of age due to the
inappropriate composition and volume (see paragraphs 4.4, 5.1 and 5.2 of the SmPC).
Do not exceed the maximum daily dose reported below. Due to the static composition
of the multi-compartment bag, it may not be possible to simultaneously satisfy
all of the patient's nutritional requirements. Clinical situations may occur in which patients
require varying amounts of nutrients compared to the composition of the static bag. In such
situations, any adjustment of the volume (dose) must take into consideration the effect
resulting from this on the dosage of all other nutrients in OLIMEL N12E. In these
circumstances, healthcare professionals may consider adjusting the volume
(dose) of OLIMEL N12E in order to meet this increased need.

In adults:
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N12E, as well as the additional energy or protein
provided orally/enterally, therefore the bag formats must be chosen accordingly.
Average daily requirements are:

• 0.16-0.35 g nitrogen/kg body weight (1-2 g of amino acids/kg), depending on the patient's nutritional status and the degree of catabolic stress. Special populations may require up to 0.4 g of nitrogen / kg of body weight (2.5 g of amino acids / kg).
• 20-40 kcal/kg,
• 20-40 mL fluids /kg or 1-1.5 mL per kcal spent.

For OLIMEL N12E, the maximum daily dose is defined by the amino acid intake, 26 mL/kg,
corresponding to 2.0 g/kg amino acids, 1.9 g/kg glucose, 0.9 g/kg lipids. For a 70 kg patient
this would be equivalent to 1820 mL of OLIMEL N12E per day, which translates into an intake of
138 g amino acids, 133 g glucose and 64 g lipids (i.e. 1171 non-protein kcal and 1723 total kcal).

In continuous renal replacement therapy (CRRT):For OLIMEL
N12E, the maximum daily dose is defined by the amino acid intake, 33 ml/ kg
corresponding to 2.5 g / kg of amino acids, 2.4 g/ kg of glucose, 1.2 g/ kg of lipids. For a 70 kg patient,
this would equate to 2310 ml of OLIMEL N12E per day, resulting in an intake of 175 g of
amino acids, 169 g of glucose and 81 g of lipids (i.e. 1486 non-protein kcal and 2187 total kcal).

In patients with pathological obesity: the dosage must be calculated based on ideal body weight (IBW). For OLIMEL N12E, the maximum daily dose is defined by the amino acid intake,
33 ml/kg of IBW corresponding to 2.5 g/kg of amino acids, 2.4 g/kg of glucose, 1.2 g/kg of lipids. For a
70 kg patient, this would equate to 2310 ml of OLIMEL N12E per day, resulting in
an intake of 175 g of amino acids, 169 g of glucose and 81 g of lipids (i.e. 1486 non-protein kcal and
2187 total kcal).

Normally, the flow rate must be increased gradually during the first hour
then must be adjusted to take into account the dose to be administered, the volumes to be taken
daily and the duration of the infusion.
For OLIMEL N12E the maximum infusion rate is 1.3 mL/kg/hour, corresponding to 0.10 g/kg/hour of
amino acids; 0.10 g/kg/hour of glucose and 0.05 g/kg/hour of lipids.

In children over 2 years of age and adolescents
No studies have been conducted in the pediatric population.
The dosage depends on energy expenditure, clinical status, body weight and the patient's ability to
metabolize the constituents of OLIMEL N12E, as well as additional energy or protein
provided orally/enterally, therefore the bag formats must be chosen accordingly.
In addition, daily fluid, nitrogen and energy requirements gradually decrease with age.
2 groups were considered, between 2 and 11 years of age, and between 12 and 18 years of age.
For Olimel N12E in the 2 to 11 year age group, amino acid and
magnesium concentrations are the limiting factors for daily dosage. In this age group, the
amino acid concentration is the limiting factor for the hourly rate.
In the 12 to 18 year age group, amino acid and magnesium concentrations are the
limiting factors for daily dosage. In this age group, amino acid concentration is the limiting factor for the hourly rate. The resulting intakes are shown below:
Normally, the flow rate must be increased gradually during the first hour and then must
be adjusted taking into account the dose to be administered, the daily volume
intake and the duration of the infusion.
In general, in young children it is recommended to start the infusion with a low daily dose, and
to increase it gradually up to the maximum dosage (see above).
The maximum infusion rate is 2.6 ml/kg/hour in children between 2 and 11 years of age and 1.6
ml/kg/hour in children between 12 and 18 years of age.
Method and duration of administration
For single use only.
It is recommended to use the contents immediately after opening the bag and not
to store it for a subsequent infusion.
After reconstitution, the mixture is homogeneous and has a milky appearance.
For instructions on the preparation and handling of the infusion emulsion, see paragraph

• 6.6 of the Summary of Product Characteristics.

Due to its high osmolarity, OLIMEL N12E must be administered only through a central vein.
The recommended infusion duration for a parenteral nutrition bag is between 12 and 24
hours.
Treatment with parenteral nutrition may continue for as long as required by the patient's clinical condition.

• H.INCOMPATIBILITIESDo not add any other medicine or substances to any of the bag constituents or to the reconstituted emulsion without first verifying the compatibility and stability of the resulting preparation (in particular the stability of the lipid emulsion).

Incompatibilities can arise, for example, from excessive acidity (low pH) or from an inappropriate content of divalent cations (Ca and Mg) which can destabilize the lipid emulsion.
As with any other parenteral nutrition mixture, the calcium/phosphate ratio must be considered.
Excessive addition of calcium and phosphate, especially in the form of mineral salts, can cause the formation of calcium phosphate precipitates.
OLIMEL N12E contains calcium ions which represent a further risk of coagulation in blood
or in blood components anticoagulated or preserved with citrate.
Ceftriaxone must not be mixed or administered concurrently with intravenous solutions
containing calcium, including OLIMEL N12E, through the same infusion line (e.g. via a
Y-connector) due to the risk of ceftriaxone-calcium salt precipitation (see paragraphs

• 4.4 and 4.5 of the SmPC). Ceftriaxone and solutions containing calcium can be administered sequentially if different infusion lines are used or if the infusion lines have been thoroughly flushed with saline between infusions to avoid precipitate formation. Due to the risk of precipitation, OLIMEL N12E must not be administered through the same infusion line or mixed with the antibiotic ampicillin or the antiepileptic phenytoin.

Verify compatibility with solutions administered simultaneously through the same
infusion set, catheter or cannula.
Do not administer before, concurrently or after a blood transfusion through the same line,
due to the risk of pseudoagglutination.

• I.SPECIAL PRECAUTIONS FOR DISPOSAL AND HANDLING

An overview of the various stages of preparation for the administration of OLIMEL N12E is
illustrated in Figure 1.
Opening
Remove the external protective wrapper.
Discard the oxygen absorber bag.
Check the integrity of the bag and the non-permanent separation membranes. Use only if the
bag is undamaged, if the non-permanent separation membranes are intact (i.e. no
mixing of the contents of the 3 compartments), if the amino acid solution and the
glucose solution are clear, colorless or slightly yellow, and practically free of visible particles,
and if the lipid emulsion is a homogeneous liquid with a milky appearance.
Mixing of the solutions and the emulsion
Make sure the product is at room temperature when breaking the non-permanent
separation membranes.
Roll the bag manually on itself, starting from the top (end with loop). The
non-permanent separation membranes will disappear from the side next to the openings. Continue
to roll the bag until the separation membranes are open for about half their
length.
Mix the bag by inverting it at least 3 times.
After reconstitution the mixture is a homogeneous emulsion with a milky appearance.
Additives:
The bag is equipped with sufficient capacity to allow for additives, such as vitamins, electrolytes and
trace elements.
Any addition (including vitamins) should be made to the reconstituted mixture (after opening the
non-permanent separation membranes and after mixing the contents of the three
compartments).
Vitamins can also be added to the glucose compartment before the mixture is
reconstituted (before opening the non-permanent separation membranes and before
mixing the three compartments).
Additives must be made by qualified personnel under aseptic conditions.
The OLIMEL N12E formulation can be supplemented with electrolytes, inorganic/organic phosphate
and with commercially available multi-vitamin (such as Cernevit) and multi-
trace element preparations (such as Nutryelt). The maximum total levels of additives for listed in the following table
have been demonstrated by stability data and should not be considered dosage recommendations. Supplementation should be dictated by the patient's clinical needs and should not
exceed nutritional guidelines. Electrolytes already present in the bag should be taken
into consideration when reaching the total maximum level.
Compatibility may vary between products from different sources and healthcare professionals are
advised to perform appropriate checks when mixing OLIMEL N12E with other parenteral solutions.

When making additions, measure the final osmolarity of the mixture before administration by peripheral vein.
To make an addition:

• Operate under aseptic conditions.
• Prepare the injection point of the bag.
• Puncture the injection point and inject the additives using a needle or a reconstitution device.
• Mix the contents of the bag and the additives.

responsibility of the user and should normally not exceed 24 hours at 2-8 °C, unless
reconstitution has occurred under controlled and validated aseptic conditions.

Validity After Addition of Supplements:
For specific mixtures, chemical and physical stability during use has been demonstrated for 7 days at 2°C - 8°C,
followed by 48 hours at a temperature not exceeding 30°C.
From a microbiological point of view, any mixture must be used immediately. Otherwise, the storage times and conditions during use after mixing and before use are
the responsibility of the user and should not normally exceed 24 hours, at 2°C- 8°C, unless
the addition of supplements has occurred under controlled and validated aseptic conditions.
Infusion Preparation
The operation must be carried out under aseptic conditions.
Suspend the bag.
Remove the plastic protection from the administration point.
Firmly insert the spike of the infusion set into the administration point.

Figure 1. Procedure for administering OLIMEL

Administration
For single use only
Administer the product only after breaking the non-permanent separation membranes between the 3
compartments and mixing the contents of the 3 compartments.
Ensure that the final emulsion for infusion does not show evidence of phase separation.
After opening the bag, the contents must be used immediately. Never store the bag
open for a subsequent infusion.
Do not reconnect any partially used bags.
Do not connect the bags in series to avoid the possibility of gaseous embolism due to the gas contained
in the main bag.
Dispose of any unused product, any derived waste and all necessary devices.
Extravasation
The catheter site must be checked regularly for possible signs of extravasation.
In case of extravasation, administration must be stopped immediately while maintaining the
catheter or cannula inserted for immediate patient treatment. If possible, perform
aspiration through the inserted catheter or cannula to reduce the amount of fluid present
in the tissues before removing the catheter or cannula.
Depending on the extravasated product (including one or more products mixed with OLIMEL N12E, if
applicable) and the extent or degree of a possible lesion, appropriate specific measures must be taken.
Treatment options may include non-
pharmacological, pharmacological and/or surgical intervention. In case of large-scale extravasation, consult the
plastic surgeon within the first 72 hours.
The extravasation site should be monitored at least every 4 hours during the first 24 hours, then
once a day.
The infusion should not be restarted in the same central vein.